Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005739 mitochondrion	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Correct but general mitochondrial localization inferred phylogenetically. The more specific inner-membrane and prohibitin-complex localizations are experimentally supported and separately annotated, so this broad term is retained as non-core. Reason: phb-1 is a bona fide mitochondrial protein, so the term is not wrong, but GO:0005743 (mitochondrial inner membrane) and GO:0035632 (mitochondrial prohibitin complex) are the informative, experimentally supported localizations for this subunit.
GO:0007005 mitochondrion organization	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic inference that phb-1 acts in mitochondrion organization, corroborated by experimental (IMP) and author-statement (NAS) annotations for the same term. A core process for this gene. Reason: Consistent with the experimentally demonstrated requirement of the PHB complex for normal mitochondrial biogenesis/organization. Supporting Evidence: PMID:12794069 a deficiency in PHB proteins results in altered mitochondrial biogenesis in body wall muscle cells
GO:0002082 regulation of oxidative phosphorylation	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Electronic (ARBA) annotation that mirrors the experimental WB IMP annotation to the same term. Biologically defensible given the conserved role of prohibitins in stabilizing respiratory-chain subunits, but it is a downstream consequence of complex loss rather than a dedicated phb-1 activity. Reason: Redundant electronic echo of the experimental IMP annotation (PMID:12794069); effect on oxidative phosphorylation is an indirect consequence of losing an essential inner-membrane complex, so it is non-core.
GO:0005743 mitochondrial inner membrane	IEA GO_REF:0000044	ACCEPT	Summary: Electronic subcellular-location mapping to the mitochondrial inner membrane, independently confirmed by experimental IDA evidence. This is the correct, core localization of the PHB complex. Reason: The inner-membrane localization is experimentally established (see the ComplexPortal IDA annotation) and matches the UniProt SUBCELLULAR LOCATION. Supporting Evidence: PMID:12794069 prohibitins in C. elegans form a high molecular weight complex in the mitochondrial inner membrane similar to that of yeast and humans
GO:0006979 response to oxidative stress	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Electronic (ARBA) annotation mirroring the WB IMP annotation. Altered oxidative-stress sensitivity is a plausible but indirect consequence of impaired mitochondrial function in prohibitin-depleted animals. Reason: Redundant with the experimental IMP annotation (PMID:12794069); pleiotropic downstream phenotype of an essential mitochondrial gene, not a core function.
GO:0007283 spermatogenesis	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Electronic (ARBA) annotation mirroring the WB IMP germline phenotype. Reason: Redundant with the experimental IMP annotation (PMID:12794069); germline/ spermatogenesis defects are a pleiotropic consequence of depleting an essential mitochondrial complex, not a dedicated phb-1 function.
GO:0008406 gonad development	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Electronic (ARBA) annotation mirroring the WB IMP gonad phenotype. Reason: Redundant with the experimental IMP annotation (PMID:12794069); pleiotropic developmental consequence of losing the essential PHB complex.
GO:0009792 embryo development ending in birth or egg hatching	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Electronic (ARBA) annotation mirroring the WB IMP embryonic-lethality phenotype. Reason: Redundant with the experimental IMP annotation (PMID:12794069); embryonic arrest reflects the essentiality of the complex rather than a dedicated embryogenesis function of phb-1.
GO:0016020 membrane	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Generic InterPro-to-GO membrane localization. Uninformative given that the specific mitochondrial inner-membrane localization is experimentally established. Reason: GO:0016020 (membrane) is an over-general parent; the informative and correct localization GO:0005743 (mitochondrial inner membrane) is already annotated.
GO:0030421 defecation	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Electronic (ARBA) annotation mirroring the WB IMP behavioural phenotype. Reason: Redundant with the experimental IMP annotation (PMID:12794069); altered defecation is a pleiotropic behavioural consequence of mitochondrial dysfunction, not a core molecular role.
GO:0040018 positive regulation of multicellular organism growth	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Electronic (ARBA) annotation mirroring the WB IMP body-size/growth phenotype. Reason: Redundant with the experimental IMP annotation (PMID:12794069); reduced growth on prohibitin depletion is a systemic consequence of impaired mitochondrial function, not a dedicated function.
GO:0043051 regulation of nematode pharyngeal pumping	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Electronic (ARBA) annotation mirroring the WB IMP behavioural phenotype. Reason: Redundant with the experimental IMP annotation (PMID:12794069); pharyngeal pumping change is a pleiotropic behavioural consequence, not a core function.
GO:0048477 oogenesis	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Electronic (ARBA) annotation mirroring the WB IMP germline phenotype. Reason: Redundant with the experimental IMP annotation (PMID:12794069); oogenesis defects are a pleiotropic consequence of losing the essential PHB complex.
GO:0005743 mitochondrial inner membrane	IDA PMID:26092086 Analysis of the effect of the mitochondrial prohibitin compl...	ACCEPT	Summary: Direct experimental evidence (ComplexPortal curation) that the PHB complex, of which phb-1 is a subunit, resides in the mitochondrial inner membrane. Core localization. Reason: Established inner-membrane localization; the heterodimer assembles into a ring embedded in the inner mitochondrial membrane. Supporting Evidence: PMID:26092086 which bind to each other to form a heterodimer that is assembled into a ring-like macromolecular structure at the inner mitochondrial membrane
GO:0007005 mitochondrion organization	NAS PMID:26092086 Analysis of the effect of the mitochondrial prohibitin compl...	ACCEPT	Summary: Author-stated involvement of the PHB complex in mitochondrion organization, consistent with the experimental IMP annotation. Core process. Reason: Prohibitin depletion perturbs mitochondrial biogenesis/organization; a well-supported core role. Supporting Evidence: PMID:12794069 a deficiency in PHB proteins results in altered mitochondrial biogenesis in body wall muscle cells
GO:0035632 mitochondrial prohibitin complex	IDA PMID:26092086 Analysis of the effect of the mitochondrial prohibitin compl...	ACCEPT	Summary: Direct evidence that phb-1 is part of the mitochondrial prohibitin complex. This complex membership is the defining, primary core annotation for phb-1. Reason: phb-1 and phb-2 form the obligate ring complex; membership is experimentally established and the two subunits are interdependent for its formation. Supporting Evidence: PMID:26092086 These two subunits are interdependent for the formation of the complex, leading the absence of one of them to the absence of the whole complex
GO:0050821 protein stabilization	NAS PMID:26092086 Analysis of the effect of the mitochondrial prohibitin compl...	ACCEPT	Summary: Author-stated role of the PHB complex as a membrane-bound chaperone that holds and stabilizes newly synthesized mitochondrial-encoded proteins. This is the closest capture of the complex's candidate molecular role, though it is a proposed (largely yeast/human-derived) function rather than one biochemically demonstrated in worm. Reason: Represents the proposed complex-level chaperone/holdase activity; retained as a candidate core function, with the caveat that the true molecular mechanism remains debated (see knowledge_gaps). Supporting Evidence: PMID:26092086 a membrane-bound chaperone, which holds and stabilizes newly synthesised mitochondrial-encoded proteins
GO:0035632 mitochondrial prohibitin complex	IPI PMID:19812672 Prohibitin couples diapause signalling to mitochondrial meta...	ACCEPT	Summary: Physical-interaction evidence (with phb-2, WB:WBGene00004015) that phb-1 is part of the mitochondrial prohibitin complex. Direct support for the obligate phb-1/phb-2 partnership. Reason: Confirms the direct phb-1/phb-2 interaction that constitutes the ring complex; a defining core annotation. Supporting Evidence: PMID:19812672 form a ring-like, high-molecular-mass complex at the inner membrane of mitochondria
GO:0002082 regulation of oxidative phosphorylation	IMP PMID:12794069 The mitochondrial prohibitin complex is essential for embryo...	KEEP AS NON CORE	Summary: Experimental (RNAi) evidence linking prohibitin depletion to altered oxidative phosphorylation, consistent with the conserved role of the complex in stabilizing respiratory-chain subunits. An indirect, non-core consequence of losing the essential complex. Reason: Full-text-based experimental annotation (retained, not removed); effect on oxidative phosphorylation reflects downstream respiratory-chain destabilization rather than a dedicated regulatory activity of phb-1.
GO:0006979 response to oxidative stress	IMP PMID:12794069 The mitochondrial prohibitin complex is essential for embryo...	KEEP AS NON CORE	Summary: Experimental (RNAi) evidence of altered oxidative-stress response upon prohibitin depletion. Pleiotropic consequence of mitochondrial dysfunction. Reason: Retained as an experimental annotation; oxidative-stress phenotype is an indirect consequence of impaired mitochondrial function, not a core role.
GO:0007005 mitochondrion organization	IMP PMID:12794069 The mitochondrial prohibitin complex is essential for embryo...	ACCEPT	Summary: Experimental (RNAi) evidence that prohibitin depletion alters mitochondrial biogenesis/organization in body-wall muscle. Core process for phb-1. Reason: Directly supported by the observed mitochondrial-biogenesis defect; a core function of the complex. Supporting Evidence: PMID:12794069 a deficiency in PHB proteins results in altered mitochondrial biogenesis in body wall muscle cells
GO:0007283 spermatogenesis	IMP PMID:12794069 The mitochondrial prohibitin complex is essential for embryo...	KEEP AS NON CORE	Summary: Experimental (RNAi) germline phenotype. Pleiotropic developmental consequence of depleting the essential PHB complex. Reason: Retained as an experimental annotation; germline/spermatogenesis defects follow from loss of an essential mitochondrial complex during germline differentiation rather than a dedicated spermatogenesis function. Supporting Evidence: PMID:12794069 PHB proteins are essential during embryonic development and are required for somatic and germline differentiation in the larval gonad
GO:0008406 gonad development	IMP PMID:12794069 The mitochondrial prohibitin complex is essential for embryo...	KEEP AS NON CORE	Summary: Experimental (RNAi) evidence of somatic and germline gonad differentiation defects. Pleiotropic developmental consequence. Reason: Retained as an experimental annotation; gonad-development defect reflects the essentiality of the complex in dividing/differentiating tissue, not a dedicated gonadogenesis function. Supporting Evidence: PMID:12794069 PHB proteins are essential during embryonic development and are required for somatic and germline differentiation in the larval gonad
GO:0009792 embryo development ending in birth or egg hatching	IMP PMID:12794069 The mitochondrial prohibitin complex is essential for embryo...	KEEP AS NON CORE	Summary: Experimental (RNAi) embryonic-lethality phenotype. Reflects essentiality of the PHB complex. Reason: Retained as an experimental annotation; embryonic arrest is a consequence of the complex being essential rather than a dedicated embryogenesis function of phb-1. Supporting Evidence: PMID:12794069 PHB proteins are essential during embryonic development and are required for somatic and germline differentiation in the larval gonad
GO:0030421 defecation	IMP PMID:12794069 The mitochondrial prohibitin complex is essential for embryo...	KEEP AS NON CORE	Summary: Experimental (RNAi) behavioural phenotype scored by WormBase curators from the full text. Pleiotropic consequence of mitochondrial dysfunction. Reason: Retained as an experimental annotation (curators read the full text); altered defecation is a pleiotropic behavioural readout, not a core molecular role.
GO:0031966 mitochondrial membrane	IDA PMID:12794069 The mitochondrial prohibitin complex is essential for embryo...	KEEP AS NON CORE	Summary: Direct experimental evidence of mitochondrial-membrane localization. Correct but less specific than the separately annotated mitochondrial inner membrane, so retained as non-core. Reason: The localization is correct; GO:0005743 (mitochondrial inner membrane) is the more precise term and is also annotated, so this broader term is retained but non-core. Supporting Evidence: PMID:12794069 prohibitins in C. elegans form a high molecular weight complex in the mitochondrial inner membrane similar to that of yeast and humans
GO:0040018 positive regulation of multicellular organism growth	IMP PMID:12794069 The mitochondrial prohibitin complex is essential for embryo...	KEEP AS NON CORE	Summary: Experimental (RNAi) body-size/growth phenotype. Systemic consequence of impaired mitochondrial function. Reason: Retained as an experimental annotation; reduced growth on depletion is a systemic consequence of mitochondrial dysfunction rather than a dedicated growth-promoting activity.
GO:0043051 regulation of nematode pharyngeal pumping	IMP PMID:12794069 The mitochondrial prohibitin complex is essential for embryo...	KEEP AS NON CORE	Summary: Experimental (RNAi) behavioural phenotype. Pleiotropic consequence of mitochondrial dysfunction. Reason: Retained as an experimental annotation; pharyngeal-pumping change is a pleiotropic behavioural readout, not a core molecular role.
GO:0048477 oogenesis	IMP PMID:12794069 The mitochondrial prohibitin complex is essential for embryo...	KEEP AS NON CORE	Summary: Experimental (RNAi) germline phenotype. Pleiotropic developmental consequence of depleting the essential PHB complex. Reason: Retained as an experimental annotation; oogenesis defects follow from loss of an essential mitochondrial complex during germline differentiation. Supporting Evidence: PMID:12794069 PHB proteins are essential during embryonic development and are required for somatic and germline differentiation in the larval gonad

Core Functions

phb-1 is a structural constituent of the mitochondrial prohibitin ring complex. It has no known independent catalytic activity; instead its function is to be an obligate subunit that, together with phb-2, assembles into the ring-shaped, high-molecular-weight PHB complex embedded in the mitochondrial inner membrane. The two subunits are interdependent, so phb-1 is required for the existence of the complex itself.

Molecular Function:

structural molecule activity

Cellular Locations:

mitochondrial inner membrane

In Complex:

mitochondrial prohibitin complex

Supporting Evidence:

PMID:26092086
which bind to each other to form a heterodimer that is assembled into a ring-like macromolecular structure at the inner mitochondrial membrane
PMID:26092086
These two subunits are interdependent for the formation of the complex, leading the absence of one of them to the absence of the whole complex

As part of the mitochondrial prohibitin complex, phb-1 contributes to organization of the mitochondrial inner membrane and to stabilization of newly synthesized mitochondrial-encoded proteins (a proposed membrane-bound chaperone/scaffold role), and thereby to mitochondrial biogenesis and function. Through this activity the complex acts as a context-dependent modulator of mitochondrial metabolism, fat utilization, and adult lifespan.

Directly Involved In:

mitochondrion organization protein stabilization

Cellular Locations:

mitochondrial inner membrane

In Complex:

mitochondrial prohibitin complex

Supporting Evidence:

PMID:12794069
a deficiency in PHB proteins results in altered mitochondrial biogenesis in body wall muscle cells
PMID:26092086
a membrane-bound chaperone, which holds and stabilizes newly synthesised mitochondrial-encoded proteins
PMID:19812672
the mitochondrial prohibitin complex promotes longevity by modulating mitochondrial function and fat metabolism

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

PMID:12794069

The mitochondrial prohibitin complex is essential for embryonic viability and germline function in Caenorhabditis elegans.

PMID:19812672

Prohibitin couples diapause signalling to mitochondrial metabolism during ageing in C. elegans.

PMID:26092086

Analysis of the effect of the mitochondrial prohibitin complex, a context-dependent modulator of longevity, on the C. elegans metabolome.

Suggested Experiments

Experiment: Reconstitute or affinity-purify the worm PHB ring and test in vitro holdase/ chaperone activity against candidate mitochondrial-encoded substrates versus a scaffold/lipid-organizing readout, to discriminate the proposed molecular roles.

Type: biochemical reconstitution

Experiment: Perform proximity-labeling (BioID/TurboID) and lipidomics on tagged phb-1 to map the inner-membrane protein/lipid microdomain organized by the complex.

Type: proximity proteomics / lipidomics

Experiment: Carry out epistasis and targeted metabolic-flux analysis of phb-1 depletion across wild-type, daf-2, and dietary-restricted backgrounds to localize the node responsible for the opposite longevity outcomes.

Type: genetic epistasis / metabolomics

Knowledge Gaps

What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).

Gap: The molecular mechanism of the mitochondrial prohibitin complex is unresolved. It is not established whether the complex acts primarily as a membrane-bound chaperone/holdase for newly synthesized mitochondrial-encoded proteins, as a scaffold that organizes inner-membrane proteins within a defined (cardiolipin/phospholipid) microdomain, or as a regulator of inner-membrane proteostasis (e.g. of the m-AAA protease); nor is the direct molecular activity of phb-1 as a ring subunit expressible as a specific GO molecular function.

OPEN BIOLOGYONTOLOGY MF_DARK

What is known: It is firmly established that phb-1 and phb-2 bind each other and assemble into a ring-like, high-molecular-weight complex in the mitochondrial inner membrane, that the two subunits are interdependent (loss of one abolishes the complex), and that depletion is embryonic-lethal, disrupts gonad/germline differentiation, alters mitochondrial biogenesis, and context-dependently modulates lifespan. What is NOT established is the biochemical mechanism by which the complex produces these effects.

Significance: Prohibitins are ubiquitous and essential across eukaryotes; resolving whether the complex is fundamentally a chaperone, a membrane scaffold, or a lipid/ proteostasis organizer would explain a large body of pleiotropic phenotypes and the conserved link between mitochondrial membrane organization and ageing. The absence of a GO molecular-function term for a structural ring subunit is why the gene reads as MF-dark despite rich process/localization annotation.

What would resolve it: In vitro reconstitution / structural work on the worm (or conserved) PHB ring to test holdase vs scaffold activity; lipidomic and proximity-labeling mapping of the inner-membrane microdomain the complex organizes; separation-of-function alleles that uncouple candidate activities. In parallel, an ontology term for the structural/scaffolding molecular activity of a prohibitin-type ring subunit.

Provenance (the field's own admissions):

"the true function of the mitochondrial prohibitin complex remains elusive" — PMID:26092086
"as scaffold proteins that recruit membrane proteins to a specific lipid environment" — PMID:26092086

Proposed term (ontology gap):

prohibitin complex structural constituent activity — phb-1/phb-2 and their orthologs have no adequate GO molecular-function term for their role as structural ring subunits and inner-membrane scaffolds. They are currently annotatable only at the complex/process level or with the generic 'structural molecule activity', leaving the gene MF-dark despite a well-defined cellular role.

Gap: The mechanistic basis by which the SAME reduction of the prohibitin complex produces OPPOSITE ageing outcomes is unknown - prohibitin deficiency shortens the lifespan of otherwise wild-type animals yet extends the lifespan of diapause (daf-2), dietary-restricted, and respiration/fat-metabolism-compromised animals. The metabolic node at which the complex converts genetic/nutritional context into opposite longevity responses is undefined.

OPEN BIOLOGY RESIDUAL_SUBGAP

What is known: The context-dependence itself is well documented (life-shortening in wild type vs life-extending in daf-2/DR/mitochondrial mutants), and depletion is known to change ATP levels, fat content, mitochondrial proliferation, and the whole-animal metabolome. The upstream signalling (insulin/IGF-DAF-16, dietary restriction) and the downstream metabolic readouts are mapped, but the causal molecular link through the complex is not.

Significance: This paradox is a clean, conserved example of how mitochondrial membrane organization gates lifespan in a metabolic-state-dependent manner; resolving it would connect prohibitin biology to insulin/IGF and dietary-restriction ageing pathways mechanistically.

What would resolve it: Epistasis and metabolic-flux analysis across the opposing backgrounds; identify the prohibitin-dependent metabolic step whose perturbation flips the longevity sign; test candidate mediators (fat mobilization, respiratory-chain assembly).

Provenance (the field's own admissions):

"knockdown of prohibitin promotes longevity in diapause mutants or under conditions of dietary restriction" — PMID:19812672
"while it dramatically extends the lifespan of the already long-lived daf-2(e1370) insulin receptor mutants" — PMID:26092086

Deep Research

Falcon

(phb-1-deep-research-falcon.md)

Comprehensive Research Report: *phb-1* (Prohibitin-1) in *Caenorhabditis elegans* Falcon Edison Scientific Literature 33 citations 2 artifacts 2026-07-03T21:38:36.820966

Edison artifact artifact-00 (text/markdown)

Edison artifact artifact-01 (text/markdown)

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Comprehensive Research Report: phb-1 (Prohibitin-1) in Caenorhabditis elegans

1. Gene Identity and Protein Overview

The C. elegans gene phb-1 (ORF Y37E3.9; UniProt Q9BKU4) encodes mitochondrial prohibitin complex protein 1 (PHB-1), a 32 kDa protein belonging to the evolutionarily conserved prohibitin family and the broader SPFH (stomatin/prohibitin/flotillin/HflK/C) superfamily of membrane scaffold proteins (artalsanz2009prohibitinandmitochondrial pages 1-2, artalsanz2009prohibitinandmitochondrial pages 4-5). PHB-1 contains a conserved PHB/Band_7 (SPFH) domain adjacent to an N-terminal hydrophobic membrane-anchoring region, and a C-terminal coiled-coil domain that mediates heterodimerization with PHB-2 (hernandorodriguez2018mitochondrialqualitycontrol pages 8-10, artalsanz2009prohibitinandmitochondrial pages 1-2). Both PHB-1 and PHB-2 subunits are ubiquitously and abundantly expressed in C. elegans tissues and are interdependent: depletion of either subunit results in the absence of the functional complex (artalsanz2009prohibitinandmitochondrial pages 1-2, artalsanz2009prohibitinandmitochondrial pages 2-3).

The following table summarizes the key attributes of PHB-1:

Attribute	Summary
Protein name	Mitochondrial prohibitin complex protein 1; Prohibitin-1 (PHB-1) (artalsanz2009prohibitinandmitochondrial pages 1-2, hernandorodriguez2018mitochondrialqualitycontrol pages 8-10)
Gene name	phb-1; ORF Y37E3.9 (verified against UniProt target specification; functional literature on C. elegans prohibitin complex is consistent with this identity) (artalsanz2009prohibitinandmitochondrial pages 1-2, artalsanz2009prohibitinandmitochondrial pages 2-3)
UniProt ID	Q9BKU4 (from target specification; literature supports the corresponding C. elegans prohibitin-1 identity and function) (artalsanz2009prohibitinandmitochondrial pages 1-2, artalsanz2009prohibitinandmitochondrial pages 2-3)
Organism	Caenorhabditis elegans (artalsanz2009prohibitinandmitochondrial pages 3-4, hernandorodriguez2018mitochondrialqualitycontrol pages 8-10)
Protein family	Prohibitin family; member of the SPFH/Band_7 superfamily of membrane scaffold proteins (artalsanz2009prohibitinandmitochondrial pages 4-5, hernandorodriguez2018mitochondrialqualitycontrol pages 8-10)
Key domains	Conserved PHB/SPFH (Band_7) domain with N-terminal hydrophobic/transmembrane anchor and C-terminal coiled-coil region mediating PHB-1/PHB-2 assembly (hernandorodriguez2018mitochondrialqualitycontrol pages 8-10, artalsanz2009prohibitinandmitochondrial pages 1-2)
Molecular weight	PHB-1 is ~32 kDa; PHB-2 is ~34 kDa (hernandorodriguez2018mitochondrialqualitycontrol pages 8-10, artalsanz2009prohibitinandmitochondrial pages 1-2)
Subcellular localization	Predominantly mitochondrial inner membrane (IMM), with the complex projecting into the intermembrane space/crista lumen; localization within crista-associated membrane regions is implicated in membrane organization (hernandorodriguez2018mitochondrialqualitycontrol pages 8-10, hernandorodriguez2018mitochondrialqualitycontrol pages 10-12, lange2025insituarchitecture pages 2-3)
Complex partners	Obligatory heterocomplex with PHB-2; functionally associated with m-AAA proteases, OXPHOS/ATP synthase components, OPA1/cristae machinery, ATAD3/nucleoid-associated factors, and lipid homeostasis pathways (hernandorodriguez2018mitochondrialqualitycontrol pages 16-17, hernandorodriguez2018mitochondrialqualitycontrol pages 8-10)
Complex stoichiometry	In C. elegans and earlier models, a ~1 MDa ring-like assembly of ~12–16 PHB-1/PHB-2 heterodimers was proposed; recent in situ human cryo-ET instead resolved a bell-shaped 11-subunit alternating PHB1/PHB2 assembly, refining structural understanding of prohibitin scaffolds (hernandorodriguez2018mitochondrialqualitycontrol pages 8-10, artalsanz2009prohibitinandmitochondrial pages 1-2, lange2025insituarchitecture pages 4-7, lange2025insituarchitecture pages 1-2)
Primary molecular function	Membrane-bound scaffold/chaperone rather than enzyme or transporter; stabilizes newly synthesized/assembled IMM proteins, cooperates with m-AAA proteases in membrane protein quality control, helps organize lipid microenvironments, and supports cristae architecture and respiratory chain integrity (hernandorodriguez2018mitochondrialqualitycontrol pages 8-10, artalsanz2009prohibitinandmitochondrial pages 4-5, artalsanz2009prohibitinandmitochondrial pages 3-4, artalsanz2009prohibitinandmitochondrial pages 2-3)
Key signaling pathway interactions: IIS/DAF-2	PHB depletion shortens lifespan in wild type but extends lifespan in metabolically compromised animals such as daf-2 mutants; PHB influences lipid remodeling, TAG/yolk homeostasis, and ER stress in an insulin-signaling-dependent manner (lourenco2021themitochondrialprohibitin pages 3-5, lourenco2021themitochondrialprohibitin pages 5-7, lourenco2021themitochondrialprohibitin pages 2-3)
Key signaling pathway interactions: TORC2/SGK-1	SGK-1 is a major downstream determinant of the prohibitin longevity phenotype; PHB depletion extends lifespan in sgk-1 and rict-1 mutants, suppresses their mitochondrial and lipogenesis defects, and functionally links PHB to mTORC2-SGK-1 control of mitochondrial homeostasis (cruz‐ruiz2021prohibitindepletionextends pages 1-2, gatsi2014prohibitinmediatedlifespanand pages 8-10, cruz‐ruiz2021prohibitindepletionextends pages 2-4, cruz‐ruiz2021prohibitindepletionextends pages 13-14)
Key signaling pathway interactions: UPRmt/ATFS-1	PHB depletion robustly induces the mitochondrial unfolded protein response (UPRmt) in wild type; UPRmt behavior is context dependent in IIS/TORC2 mutants, and ATFS-1-dependent mitochondrial stress signaling contributes to longevity outcomes in PHB-deficient backgrounds (artalsanz2009prohibitinandmitochondrial pages 5-7, fernandezabascal2023twoconservedtranscription pages 4-7, fernandezabascal2023twoconservedtranscription pages 1-4, cruz‐ruiz2021prohibitindepletionextends pages 1-2)
Lifespan effects	Depletion of prohibitin shortens wild-type lifespan but extends lifespan in several metabolically compromised backgrounds including daf-2, sgk-1, and rict-1 mutants; this is one of the defining context-dependent phenotypes of the PHB complex in C. elegans aging biology (lourenco2021themitochondrialprohibitin pages 2-3, cruz‐ruiz2021prohibitindepletionextends pages 1-2, gatsi2014prohibitinmediatedlifespanand pages 1-2, gatsi2014prohibitinmediatedlifespanand pages 2-3)
Essential cellular processes	Embryonic viability, germline function, mitochondrial morphogenesis, cristae maintenance, respiratory chain/OXPHOS biogenesis, mitochondrial proteostasis, lipid homeostasis, nucleoid/mtDNA organization, and mitochondrial quality control; PHB-2 additionally serves as an IMM mitophagy receptor via LC3 interaction, whereas PHB-1 participates in the heterocomplex that supports these functions (artalsanz2009prohibitinandmitochondrial pages 3-4, hernandorodriguez2018mitochondrialqualitycontrol pages 16-17, hernandorodriguez2018mitochondrialqualitycontrol pages 8-10, wei2017prohibitin2is pages 1-3)

Table: This table summarizes the core identity, localization, molecular role, pathway interactions, and phenotypic consequences of PHB-1/prohibitin-1 in C. elegans. It is useful as a compact reference linking the prohibitin complex’s structural role in mitochondria to its context-dependent effects on metabolism, stress signaling, and longevity.

2. Structure and Complex Formation

PHB-1 and PHB-2 associate to form a large, ring-like macromolecular complex of approximately 1 MDa at the mitochondrial inner membrane (hernandorodriguez2018mitochondrialqualitycontrol pages 8-10, artalsanz2009prohibitinandmitochondrial pages 1-2). Earlier biochemical studies estimated that this complex consists of 12–16 PHB-1/PHB-2 heterodimeric building blocks with a diameter of 20–25 nm (artalsanz2009prohibitinandmitochondrial pages 1-2, artalsanz2009prohibitinandmitochondrial pages 3-4). PHB-1 is anchored at the membrane surface via its N-terminal hydrophobic region, while PHB-2 contains a true transmembrane domain (artalsanz2009prohibitinandmitochondrial pages 1-2).

A landmark structural advance was reported by Lange et al. (2025), who used cryo-electron tomography and subtomogram averaging to determine the in situ architecture of the human prohibitin complex within intact mitochondria. This study revealed a bell-shaped structure consisting of 11 alternating PHB1 and PHB2 molecules (either 6PHB1/5PHB2 or 5PHB1/6PHB2), with a diameter of approximately 190 Å and a height of 84 Å (lange2025insituarchitecture pages 4-7, lange2025insituarchitecture pages 1-2). The N-terminal transmembrane domains anchor the complex in the lipid bilayer, while the C-terminal coiled-coil domains converge at the top of the bell through electrostatic interactions (lange2025insituarchitecture pages 4-7). The study further revealed an average of approximately 43 prohibitin complexes per crista, covering 1–3% of the cristae membrane surface (lange2025insituarchitecture pages 1-2). These structures are enriched at crista membranes and project toward the intermembrane space/crista lumen (lange2025insituarchitecture pages 2-3). This revised stoichiometry (11 subunits rather than 12–16 heterodimers) refines our understanding of prohibitin architecture, though the C. elegans complex stoichiometry has not been independently resolved at this level.

3. Subcellular Localization

PHB-1 localizes primarily to the inner mitochondrial membrane (IMM), where the complex projects into the intermembrane space (hernandorodriguez2018mitochondrialqualitycontrol pages 8-10, hernandorodriguez2018mitochondrialqualitycontrol pages 10-12, lange2025insituarchitecture pages 2-3). The complex is part of the ER-mitochondria organizing network (ERMIONE), which links the endoplasmic reticulum and both mitochondrial membranes to maintain membrane architecture and homeostasis (hernandorodriguez2018mitochondrialqualitycontrol pages 10-12). PHB-1 has also been reported to interact transiently with peroxisomal and lipid droplet proteins, though its predominant site of action is the IMM (hernandorodriguez2018mitochondrialqualitycontrol pages 10-12). In C. elegans, PHB-1 and PHB-2 are particularly required in tissues with high energy demands and actively proliferating cells, including the germline and body-wall muscle (artalsanz2009prohibitinandmitochondrial pages 3-4).

4. Primary Molecular Function

PHB-1 is not an enzyme, transporter, or signaling receptor. Rather, it functions as a membrane-bound scaffold and holdase/unfoldase-type chaperone within the inner mitochondrial membrane (hernandorodriguez2018mitochondrialqualitycontrol pages 8-10, artalsanz2009prohibitinandmitochondrial pages 4-5, artalsanz2009prohibitinandmitochondrial pages 3-4). Its precise biochemical activity has remained challenging to define, but converging evidence supports several interrelated functions:

4.1. Membrane Protein Quality Control and OXPHOS Complex Assembly

PHB-1 physically interacts with mitochondrial m-AAA proteases (including SPG7 and AFG3L1/2) and modulates their activity (hernandorodriguez2018mitochondrialqualitycontrol pages 8-10, hernandorodriguez2018mitochondrialqualitycontrol pages 16-17). The PHB complex protects newly imported and newly synthesized OXPHOS subunits—particularly the highly hydrophobic mitochondrial-encoded subunits of complexes I and IV—from premature protease-mediated degradation, acting as a holdase-type chaperone until proper assembly with nuclear-encoded counterparts can occur (hernandorodriguez2018mitochondrialqualitycontrol pages 8-10, artalsanz2009prohibitinandmitochondrial pages 4-5, artalsanz2009prohibitinandmitochondrial pages 3-4). PHB-1 also associates with ATP synthase subunits, and its loss affects respiratory supercomplex formation (hernandorodriguez2018mitochondrialqualitycontrol pages 16-17, lourenco2021themitochondrialprohibitin pages 12-13).

4.2. Cristae Morphogenesis and OPA1 Regulation

The PHB complex stabilizes long isoforms of OPA1 (the C. elegans ortholog is EAT-3), which are essential for mitochondrial inner membrane fusion and cristae junction formation (hernandorodriguez2018mitochondrialqualitycontrol pages 8-10, hernandorodriguez2018mitochondrialqualitycontrol pages 16-17, artalsanz2009prohibitinandmitochondrial pages 4-5). Loss of prohibitins leads to aberrant OPA1 processing, disrupted cristae architecture, and severe mitochondrial fragmentation—transforming normal tubular elongated mitochondria into fragmented structures, as observed in C. elegans body-wall muscle (artalsanz2009prohibitinandmitochondrial pages 3-4, hernandorodriguez2018mitochondrialqualitycontrol pages 8-10). PHB keeps the OMA1 protease in check; loss of PHB releases OMA1 to cleave OPA1 into short isoforms, driving fragmentation (artalsanz2009prohibitinandmitochondrial pages 2-3).

4.3. Membrane Lipid Organization

PHB-1 functions as a membrane organizer that clusters specific lipids at defined sites within the IMM. Genetic and biochemical evidence demonstrates interactions between prohibitins and the metabolism of cardiolipin and phosphatidylethanolamine (PE), two key mitochondrial phospholipids (hernandorodriguez2018mitochondrialqualitycontrol pages 8-10, hernandorodriguez2018mitochondrialqualitycontrol pages 16-17). Loss of PHB complexes alters cardiolipin acylation and affects cholesterol biosynthesis, linking prohibitin to membrane lipid homeostasis (hernandorodriguez2018mitochondrialqualitycontrol pages 8-10). The PHB/SPFH domain itself may mediate lipid binding, though this has not been definitively demonstrated biochemically (artalsanz2009prohibitinandmitochondrial pages 4-5).

4.4. Mitochondrial Nucleoid Organization and mtDNA Maintenance

PHB-1 associates with mitochondrial nucleoids, the protein-DNA complexes that package mtDNA, together with TFAM, mtSSB, and ATAD3 (hernandorodriguez2018mitochondrialqualitycontrol pages 8-10). Both PHB subunits co-purify with tagged mitochondrial DNA-binding proteins, and depletion of either PHB or ATAD3 dramatically reduces mitochondrial protein synthesis (hernandorodriguez2018mitochondrialqualitycontrol pages 8-10). In mouse neurons, loss of PHB2 destabilizes the mitochondrial genome and leads to respiratory deficiencies, demonstrating that prohibitin scaffolds are required for mtDNA maintenance (hernandorodriguez2018mitochondrialqualitycontrol pages 16-17, lourenco2021themitochondrialprohibitin pages 12-13).

4.5. Mitophagy (via PHB-2)

While PHB-1 itself does not directly bind LC3, its obligate partner PHB-2 has been identified as an inner mitochondrial membrane mitophagy receptor. PHB-2 binds LC3-II through an LC3-interacting region (LIR) motif upon proteasome-dependent rupture of the outer mitochondrial membrane, facilitating Parkin-mediated mitophagy (wei2017prohibitin2is pages 12-13, wei2017prohibitin2is pages 1-3, wei2017prohibitin2is pages 4-5). PHB-1 interacts with LC3-II indirectly through the PHB-1/PHB-2 complex (lahiri2017phb2prohibitin2an pages 1-2). In C. elegans, PHB-2 is essential for clearing paternal mitochondria during embryogenesis, contributing to maternal mitochondrial inheritance (wei2017prohibitin2is pages 12-13, qi2023essentialproteinphb2 pages 5-6). A PINK1-dependent pathway involving PARL and PGAM5 further connects the PHB complex to mitophagy regulation (qi2023essentialproteinphb2 pages 5-6, belser2021roleofprohibitins pages 1-2).

5. Biological Processes and Signaling Pathways

5.1. Essential Role in Development and Germline Function

In C. elegans, homozygous phb-1 and phb-2 deletion mutants are embryonic lethal; animals that develop from heterozygous mothers (due to maternal contribution of PHB protein) grow into sterile adults with severely compromised germline function and strongly induced mitochondrial unfolded protein response (UPRmt) (hernandorodriguez2018mitochondrialqualitycontrol pages 8-10, hernandorodriguez2018mitochondrialqualitycontrol pages 16-17). Post-embryonic depletion impairs germline function with reduced oocyte production (artalsanz2009prohibitinandmitochondrial pages 3-4).

5.2. Context-Dependent Modulation of Lifespan

One of the most striking and extensively studied phenotypes of PHB-1 is its paradoxical, context-dependent effect on lifespan. PHB depletion shortens the lifespan of wild-type C. elegans but dramatically extends the lifespan of metabolically compromised mutants, including insulin/IGF-1 signaling (IIS) receptor daf-2 mutants, TORC2 pathway mutants sgk-1 and rict-1, and dietary-restricted animals (fernandezabascal2023twoconservedtranscription pages 4-7, lourenco2021themitochondrialprohibitin pages 2-3, cruz‐ruiz2021prohibitindepletionextends pages 1-2, gatsi2014prohibitinmediatedlifespanand pages 1-2, gatsi2014prohibitinmediatedlifespanand pages 2-3). This paradox has been a major focus of C. elegans* aging research and is summarized in the table below:

Genetic Background	Lifespan Effect of PHB Depletion	UPRmt Response	Mechanism/Notes	Key Reference
Wild-type	Shortens lifespan (fernandezabascal*2023twoconservedtranscription pages 4-7, lourenco2021themitochondrialprohibitin pages 5-7, lourenco2021themitochondrialprohibitin pages 2-3, gatsi2014prohibitinmediatedlifespanand pages 1-2)	Strongly induced (fernandezabascal2023twoconservedtranscription pages 4-7, fernandezabascal2023twoconservedtranscription pages 1-4, artalsanz2009prohibitinandmitochondrial pages 5-7)	PHB loss disrupts mitochondrial membrane organization and proteostasis, induces mitochondrial stress, and is generally detrimental in metabolically normal animals (hernandorodriguez2018mitochondrialqualitycontrol pages 8-10, artalsanz2009prohibitinandmitochondrial pages 4-5)	Gatsi et al. 2014; Fernández-Abascal et al. 2025; Lourenço & Artal-Sanz 2021 (fernandezabascal*2023twoconservedtranscription pages 4-7, lourenco2021themitochondrialprohibitin pages 2-3, gatsi2014prohibitinmediatedlifespanand pages 1-2)
daf-2(e1370)	Extends lifespan (fernandezabascal*2023twoconservedtranscription pages 4-7, lourenco2021themitochondrialprohibitin pages 5-7, lourenco2021themitochondrialprohibitin pages 2-3, gatsi2014prohibitinmediatedlifespanand pages 1-2)	Suppressed/attenuated relative to PHB-depleted wild type (fernandezabascal2023twoconservedtranscription pages 4-7, fernandezabascal2023twoconservedtranscription pages 1-4, gatsi2014prohibitinmediatedlifespanand pages 1-2)	Canonical example of context dependence: defective IIS buffers some PHB-loss consequences; longevity links to altered lipid/energy metabolism and requires mitochondrial stress signaling components including ATFS-1 in recent work (fernandezabascal*2023twoconservedtranscription pages 4-7, lourenco2021themitochondrialprohibitin pages 3-5, lourenco2021themitochondrialprohibitin pages 5-7)	Gatsi et al. 2014; Fernández-Abascal et al. 2025; Lourenço & Artal-Sanz 2021 (fernandezabascal*2023twoconservedtranscription pages 4-7, lourenco2021themitochondrialprohibitin pages 3-5, gatsi2014prohibitinmediatedlifespanand pages 1-2)
sgk-1(ok538)	Extends lifespan (reported ~18% in one study) (cruz‐ruiz2021prohibitindepletionextends pages 1-2, gatsi2014prohibitinmediatedlifespanand pages 3-4, gatsi2014prohibitinmediatedlifespanand pages 2-3)	Induced in sgk-1 mutants, but PHB depletion-associated longevity is accompanied by suppressed UPRmt relative to PHB-depleted wild type; later work also shows lifespan extension requires UPRmt and autophagy (gatsi2014prohibitinmediatedlifespanand pages 1-2, cruz‐ruiz2021prohibitindepletionextends pages 2-4)	PHB depletion suppresses sgk-1 mitochondrial, lipogenesis, yolk/lipoprotein, ROS, and oxygen-consumption defects; indicates strong interaction with TORC2/SGK-1 and membrane-lipid homeostasis (cruz‐ruiz2021prohibitindepletionextends pages 1-2, cruz‐ruiz2021prohibitindepletionextends pages 2-4, cruz‐ruiz2021prohibitindepletionextends pages 13-14)	Gatsi et al. 2014; de la Cruz-Ruiz et al. 2021 (cruz‐ruiz2021prohibitindepletionextends pages 1-2, gatsi2014prohibitinmediatedlifespanand pages 1-2, cruz‐ruiz2021prohibitindepletionextends pages 2-4)
rict-1(ft7)	Extends lifespan (gatsi2014prohibitinmediatedlifespanand pages 1-2, gatsi2014prohibitinmediatedlifespanand pages 2-3)	UPRmt regulation parallels sgk-1; rict-1 loss suppresses PHB depletion-associated UPRmt and interacts with SGK-1 in a pathway parallel to DAF-2 (gatsi2014prohibitinmediatedlifespanand pages 8-10, gatsi2014prohibitinmediatedlifespanand pages 1-2, gatsi2014prohibitinmediatedlifespanand pages 2-3)	Supports model that mTORC2/RICT-1-SGK-1 signaling is a major determinant of whether PHB depletion is pro- or anti-longevity (gatsi2014prohibitinmediatedlifespanand pages 8-10, gatsi2014prohibitinmediatedlifespanand pages 6-8, gatsi2014prohibitinmediatedlifespanand pages 2-3)	Gatsi et al. 2014 (gatsi2014prohibitinmediatedlifespanand pages 8-10, gatsi2014prohibitinmediatedlifespanand pages 1-2, gatsi2014prohibitinmediatedlifespanand pages 2-3)
Dietary restricted animals	Extends lifespan (lourenco2021themitochondrialprohibitin pages 2-3)	Not specified directly in the cited review excerpt (lourenco2021themitochondrialprohibitin pages 2-3)	Lourenço & Artal-Sanz summarize that PHB depletion can extend lifespan in dietary restriction contexts, reinforcing that PHB effects depend on systemic metabolic state rather than PHB acting as a simple pro- or anti-aging factor (lourenco2021themitochondrialprohibitin pages 2-3, lourenco2021themitochondrialprohibitin pages 7-8)	Lourenço & Artal-Sanz 2021 (lourenco2021themitochondrialprohibitin pages 2-3, lourenco2021themitochondrialprohibitin pages 7-8)

Table: This table summarizes how prohibitin depletion has opposite effects on lifespan depending on the C. elegans genetic or metabolic background. It is useful for quickly comparing longevity outcomes, UPRmt behavior, and the major mechanistic interpretations across key studies.

5.3. Insulin/IGF-1 Signaling (IIS) Pathway

PHB functionally interacts with the IIS pathway at multiple levels. Among the three kinases downstream of DAF-2 (the insulin/IGF-1 receptor), only loss of SGK-1 recapitulates the lifespan extension observed in daf-2 mutants upon PHB depletion (gatsi2014prohibitinmediatedlifespanand pages 1-2, gatsi2014prohibitinmediatedlifespanand pages 3-4). PHB depletion in daf-2 mutants extends lifespan while attenuating the UPRmt, suggesting a mitochondrial threshold effect where reduced insulin signaling protects against the deleterious consequences of PHB loss (fernandezabascal2023twoconservedtranscription pages 4-7, fernandezabascal2023twoconservedtranscription pages 1-4). PHB depletion also alters glycerolipid and triacylglyceride (TAG) pools in an IIS-dependent manner (lourenco2021themitochondrialprohibitin pages 3-5).

5.4. TORC2/SGK-1 Signaling

SGK-1 receives input from RICT-1/mTORC2, and both operate in a pathway parallel to DAF-2 for the PHB-mediated lifespan phenotype (gatsi2014prohibitinmediatedlifespanand pages 8-10, gatsi2014prohibitinmediatedlifespanand pages 1-2, gatsi2014prohibitinmediatedlifespanand pages 2-3). sgk-1 mutants exhibit impaired mitochondrial homeostasis, lipogenesis, and yolk formation due to membrane lipid and sterol homeostasis alterations; remarkably, all these defects are suppressed by PHB depletion (cruz‐ruiz2021prohibitindepletionextends pages 1-2). PHB depletion in sgk-1 mutants normalizes mitochondrial size, reduces excessive oxygen consumption and ROS levels, and restores mitochondrial morphology from abnormally swollen to normal architecture (cruz‐ruiz2021prohibitindepletionextends pages 2-4). The lifespan extension in sgk-1 mutants upon PHB depletion requires both the UPRmt and autophagy, but not mitophagy (cruz‐ruiz2021prohibitindepletionextends pages 1-2, cruz‐ruiz2021prohibitindepletionextends pages 2-4). The lipid metabolism transcription factor SREBP1/SBP-1 is also required for lifespan extension (cruz‐ruiz2021prohibitindepletionextends pages 1-2).

5.5. Mitochondrial Unfolded Protein Response (UPRmt)

PHB depletion is a potent inducer of the UPRmt in wild-type animals, activating mitochondrial chaperone genes such as hsp-6 through the transcription factor ATFS-1 (artalsanz2009prohibitinandmitochondrial pages 4-5, artalsanz2009prohibitinandmitochondrial pages 5-7, fernandezabascal2023twoconservedtranscription pages 4-7, fernandezabascal2023twoconservedtranscription pages 1-4, gatsi2014prohibitinmediatedlifespanand pages 8-10). However, the relationship between UPRmt induction and lifespan is complex: in daf-2 mutants, PHB depletion extends lifespan while paradoxically attenuating the UPRmt relative to PHB-depleted wild type (fernandezabascal2023twoconservedtranscription pages 4-7, fernandezabascal2023twoconservedtranscription pages 1-4). A recent genome-wide double RNAi screen identified two new transcription factors, ZNF-622 and TLF-1, as specific regulators of the PHB-mediated mitochondrial stress response, as well as the histone deubiquitinase USP-48 as a differential modulator of the UPRmt and aging in wild-type versus IIS mutant backgrounds (fernandezabascal*2023twoconservedtranscription pages 4-7).

5.6. Fat Metabolism and Metabolic Reprogramming

PHB modulates fat content and fatty acid composition, with a trend toward increased shorter/monounsaturated fatty acids and decreased longer/polyunsaturated fatty acids upon PHB depletion (lourenco2021themitochondrialprohibitin pages 2-3). The complex also regulates sphingolipids (sphingomyelin, ceramide) and glycerophospholipids (phosphatidylcholine, phosphatidylethanolamine) in a genetic background-dependent manner (lourenco2021themitochondrialprohibitin pages 2-3). PHB depletion affects carbohydrate and amino acid metabolism, the TCA cycle, and trehalose accumulation, demonstrating broad effects on the C. elegans metabolic network (lourenco2021themitochondrialprohibitin pages 5-7). PHB interacts with the fat mobilization regulator NHR-49 and the fatty acid desaturase FAT-7 (lourenco2021themitochondrialprohibitin pages 7-8). PHB depletion also induces ER stress in wild-type worms, but daf-2 mutants are protected from this ER stress, providing a mechanistic link between PHB, mitochondrial function, ER homeostasis, and IIS signaling (lourenco2021themitochondrialprohibitin pages 3-5, lourenco2021themitochondrialprohibitin pages 5-7).

6. Evolutionary Conservation and Structural Insights

Prohibitins are among the most highly conserved eukaryotic proteins, with orthologs in yeast, nematodes, insects, and mammals sharing both structural organization and core functions (artalsanz2009prohibitinandmitochondrial pages 1-2, artalsanz2009prohibitinandmitochondrial pages 4-5). The PHB/SPFH domain, the coiled-coil assembly region, and the ring-like supramolecular architecture are conserved features. Cross-species functional complementation experiments demonstrate that Plasmodium falciparum PHBs can complement yeast PHB mutants, underscoring deep functional conservation (artalsanz2009prohibitinandmitochondrial pages 4-5). The recently resolved in situ structure of human prohibitin (bell-shaped, 11 subunits) provides the first high-resolution architectural framework for understanding how prohibitin scaffolds organize the inner mitochondrial membrane across species (lange2025insituarchitecture pages 4-7, lange2025insituarchitecture pages 1-2).

7. Summary

PHB-1 in C. elegans is a non-enzymatic, inner mitochondrial membrane scaffold protein that forms an obligate complex with PHB-2. The PHB complex functions as a holdase/chaperone, lipid organizer, and structural scaffold essential for cristae morphogenesis, OXPHOS complex biogenesis, mitochondrial nucleoid stability, and membrane protein quality control. PHB-1 is essential for embryonic development and germline function. Its depletion induces the UPRmt and, depending on the metabolic state of the animal, either shortens or extends lifespan. The complex sits at a central nexus of nutrient-sensing pathways (IIS/DAF-2, TORC2/SGK-1) and mitochondrial stress responses (UPRmt/ATFS-1), modulating lipid metabolism, energy homeostasis, and aging in a context-dependent manner. Through its partner PHB-2, the complex also participates in mitophagy as an inner membrane receptor for LC3. The prohibitin complex thus represents one of the most functionally integrated mitochondrial regulatory assemblies studied in C. elegans biology.

References

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(wei2017prohibitin2is pages 1-3): Yongjie Wei, Wei-Chung Chiang, Rhea Sumpter, Prashant Mishra, and Beth Levine. Prohibitin 2 is an inner mitochondrial membrane mitophagy receptor. Cell, 168:224-238.e10, Jan 2017. URL: https://doi.org/10.1016/j.cell.2016.11.042, doi:10.1016/j.cell.2016.11.042. This article has 932 citations and is from a highest quality peer-reviewed journal.
(lourenco2021themitochondrialprohibitin pages 12-13): Artur B. Lourenço and Marta Artal-Sanz. The mitochondrial prohibitin (phb) complex in c. elegans metabolism and ageing regulation. Metabolites, 11:636, Sep 2021. URL: https://doi.org/10.3390/metabo11090636, doi:10.3390/metabo11090636. This article has 16 citations.
(wei2017prohibitin2is pages 12-13): Yongjie Wei, Wei-Chung Chiang, Rhea Sumpter, Prashant Mishra, and Beth Levine. Prohibitin 2 is an inner mitochondrial membrane mitophagy receptor. Cell, 168:224-238.e10, Jan 2017. URL: https://doi.org/10.1016/j.cell.2016.11.042, doi:10.1016/j.cell.2016.11.042. This article has 932 citations and is from a highest quality peer-reviewed journal.
(wei2017prohibitin2is pages 4-5): Yongjie Wei, Wei-Chung Chiang, Rhea Sumpter, Prashant Mishra, and Beth Levine. Prohibitin 2 is an inner mitochondrial membrane mitophagy receptor. Cell, 168:224-238.e10, Jan 2017. URL: https://doi.org/10.1016/j.cell.2016.11.042, doi:10.1016/j.cell.2016.11.042. This article has 932 citations and is from a highest quality peer-reviewed journal.
(lahiri2017phb2prohibitin2an pages 1-2): Vikramjit Lahiri and Daniel J Klionsky. Phb2/prohibitin 2: an inner membrane mitophagy receptor. Cell Research, 27:311-312, Feb 2017. URL: https://doi.org/10.1038/cr.2017.23, doi:10.1038/cr.2017.23. This article has 62 citations and is from a domain leading peer-reviewed journal.
(qi2023essentialproteinphb2 pages 5-6): Amanda Qi, Lillie Lamont, Evelyn Liu, Sarina D. Murray, Xiangbing Meng, and Shujie Yang. Essential protein phb2 and its regulatory mechanisms in cancer. Cells, 12:1211, Apr 2023. URL: https://doi.org/10.3390/cells12081211, doi:10.3390/cells12081211. This article has 34 citations.
(belser2021roleofprohibitins pages 1-2): Misa Belser and David W. Walker. Role of prohibitins in aging and therapeutic potential against age-related diseases. Frontiers in Genetics, Oct 2021. URL: https://doi.org/10.3389/fgene.2021.714228, doi:10.3389/fgene.2021.714228. This article has 27 citations and is from a peer-reviewed journal.
(gatsi2014prohibitinmediatedlifespanand pages 3-4): Roxani Gatsi, Bettina Schulze, María Jesús Rodríguez-Palero, Blanca Hernando-Rodríguez, Ralf Baumeister, and Marta Artal-Sanz. Prohibitin-mediated lifespan and mitochondrial stress implicate sgk-1, insulin/igf and mtorc2 in c. elegans. PLoS ONE, 9:e107671, Sep 2014. URL: https://doi.org/10.1371/journal.pone.0107671, doi:10.1371/journal.pone.0107671. This article has 55 citations and is from a peer-reviewed journal.
(gatsi2014prohibitinmediatedlifespanand pages 6-8): Roxani Gatsi, Bettina Schulze, María Jesús Rodríguez-Palero, Blanca Hernando-Rodríguez, Ralf Baumeister, and Marta Artal-Sanz. Prohibitin-mediated lifespan and mitochondrial stress implicate sgk-1, insulin/igf and mtorc2 in c. elegans. PLoS ONE, 9:e107671, Sep 2014. URL: https://doi.org/10.1371/journal.pone.0107671, doi:10.1371/journal.pone.0107671. This article has 55 citations and is from a peer-reviewed journal.
(lourenco2021themitochondrialprohibitin pages 7-8): Artur B. Lourenço and Marta Artal-Sanz. The mitochondrial prohibitin (phb) complex in c. elegans metabolism and ageing regulation. Metabolites, 11:636, Sep 2021. URL: https://doi.org/10.3390/metabo11090636, doi:10.3390/metabo11090636. This article has 16 citations.

Artifacts

Citations

artalsanz2009prohibitinandmitochondrial pages 1-2
lange2025insituarchitecture pages 4-7
lange2025insituarchitecture pages 1-2
lange2025insituarchitecture pages 2-3
hernandorodriguez2018mitochondrialqualitycontrol pages 10-12
artalsanz2009prohibitinandmitochondrial pages 3-4
artalsanz2009prohibitinandmitochondrial pages 2-3
hernandorodriguez2018mitochondrialqualitycontrol pages 8-10
artalsanz2009prohibitinandmitochondrial pages 4-5
lourenco2021themitochondrialprohibitin pages 2-3
lourenco2021themitochondrialprohibitin pages 3-5
lourenco2021themitochondrialprohibitin pages 5-7
lourenco2021themitochondrialprohibitin pages 7-8
hernandorodriguez2018mitochondrialqualitycontrol pages 16-17
gatsi2014prohibitinmediatedlifespanand pages 8-10
artalsanz2009prohibitinandmitochondrial pages 5-7
gatsi2014prohibitinmediatedlifespanand pages 1-2
gatsi2014prohibitinmediatedlifespanand pages 2-3
lourenco2021themitochondrialprohibitin pages 12-13
belser2021roleofprohibitins pages 1-2
gatsi2014prohibitinmediatedlifespanand pages 3-4
gatsi2014prohibitinmediatedlifespanand pages 6-8
https://doi.org/10.1016/j.tem.2009.04.004,
https://doi.org/10.3390/cells7120238,
https://doi.org/10.1038/s41556-025-01620-1,
https://doi.org/10.3390/metabo11090636,
https://doi.org/10.1111/acel.13359,
https://doi.org/10.1371/journal.pone.0107671,
https://doi.org/10.21203/rs.3.rs-3337719/v1,
https://doi.org/10.1016/j.cell.2016.11.042,
https://doi.org/10.1038/cr.2017.23,
https://doi.org/10.3390/cells12081211,
https://doi.org/10.3389/fgene.2021.714228,

📚 Additional Documentation

Notes

(phb-1-notes.md)

phb-1 (Caenorhabditis elegans) — research notes

UniProt: Q9BKU4 (PHB1_CAEEL). WormBase: WBGene00004014 / Y37E3.9.
Gene name: phb-1 ("Mitochondrial prohibitin complex protein 1", prohibitin-1).
275 aa; single Band_7/SPFH (prohibitin/stomatin) domain (PF01145; IPR000163);
predicted coiled coil (residues 180–213). PANTHER family PTHR23222 (PROHIBITIN),
subfamily PTHR23222:SF0 (PROHIBITIN 1). ComplexPortal CPX-4114 (Prohibitin complex).

One-line summary

phb-1 is one of the two obligate subunits (with phb-2) of the mitochondrial
prohibitin (PHB) complex, a ring-shaped, high-molecular-weight assembly in the
mitochondrial inner membrane. The complex — not the isolated subunit — is the
functional unit; loss of either subunit abolishes the whole complex.

KNOWN (well supported)

Obligate heterodimeric/ring complex with phb-2 in the mitochondrial inner
membrane. "Prohibitins in eukaryotes consist of two subunits (PHB1 and PHB2)
that together form a high molecular weight complex in the mitochondrial inner
membrane" and, in worm, "prohibitins in C. elegans form a high molecular weight
complex in the mitochondrial inner membrane similar to that of yeast and humans"
PMID:12794069.
The two subunits "bind to each other to form a heterodimer that is assembled into
a ring-like macromolecular structure at the inner mitochondrial membrane" and are
"interdependent for the formation of the complex, leading the absence of one of
them to the absence of the whole complex"
PMID:26092086
PMID:26092086.
Basis for GO:0035632 (mitochondrial prohibitin complex), GO:0005743 (mitochondrial
inner membrane). The IPI part_of annotation (PMID:19812672) is with phb-2
(WB:WBGene00004015).
Essential for embryonic viability and germline/gonad development. RNAi against
phb-1 or phb-2 "PHB proteins are essential during embryonic development and are
required for somatic and germline differentiation in the larval gonad"
PMID:12794069.
Restated later: prohibitin depletion "gives rise to a wide range of somatic and
germline defects, spanning from complete sterility to severely reduce brood sizes
and a morphologically abnormal somatic gonad"
PMID:26092086.
Basis for the WB IMP annotations to embryo development (GO:0009792), gonad
development (GO:0008406), oogenesis (GO:0048477), spermatogenesis (GO:0007283).
Altered mitochondrial biogenesis / organization on depletion. "a deficiency in
PHB proteins results in altered mitochondrial biogenesis in body wall muscle
cells" PMID:12794069.
Basis for GO:0007005 (mitochondrion organization). PHB-2 knockdown "influences ...
mitochondrial proliferation" PMID:19812672.
Context-dependent modulator of longevity, coupling to insulin/diapause signalling
and fat metabolism. "the mitochondrial prohibitin complex promotes longevity by
modulating mitochondrial function and fat metabolism in the nematode Caenorhabditis
elegans"; "prohibitin deficiency shortens the lifespan of otherwise wild-type
animals" but "knockdown of prohibitin promotes longevity in diapause mutants or
under conditions of dietary restriction"
PMID:19812672
PMID:19812672.
Later restated with genotype: "prohibitin deficiency shortens the lifespan of
otherwise wild type nematodes, while it dramatically extends the lifespan of the
already long-lived daf-2(e1370) insulin receptor mutants"
PMID:26092086.
Depletion "influences ATP levels, animal fat content and mitochondrial
proliferation in a genetic-background- and age-specific manner"
PMID:19812672.
Proposed complex-level molecular roles (from yeast/mammalian work, invoked for
the worm complex): membrane-bound chaperone that stabilizes newly synthesized
mitochondrial-encoded respiratory subunits, and/or membrane scaffold that recruits
membrane proteins to a specific lipid environment.
"The PHB complex has been shown to play a role in the stabilization of newly
synthesized subunits of mitochondrial respiratory enzymes in the yeast
Saccharomyces cerevisiae"
PMID:12794069.
"Several roles have been proposed for the mitochondrial prohibitin complex,
including a role as a membrane-bound chaperone, which holds and stabilizes newly
synthesised mitochondrial-encoded proteins ... and as scaffold proteins that
recruit membrane proteins to a specific lipid environment"
PMID:26092086
PMID:26092086.
Basis for GO:0050821 (protein stabilization, NAS). Note the qualifier: these are
proposed roles imported largely from yeast/human, not directly demonstrated
biochemically in worm.

NOT known / debated (knowledge gaps)

The molecular mechanism of the prohibitin complex is genuinely unresolved.
The 2015 metabolome paper states plainly: "the true function of the mitochondrial
prohibitin complex remains elusive"
PMID:26092086.
Whether the complex works primarily as (a) a membrane-bound chaperone/holdase for
nascent inner-membrane proteins, (b) a scaffold that organizes a specific
cardiolipin/phospholipid microdomain and recruits client membrane proteins, or
(c) a regulator of the m-AAA protease (SPG-7/paraplegin) is not settled — the
literature proposes all three but demonstrates none as the mechanism in worm.
This is both a genuine biology gap and an ontology gap: "be the structural PHB
ring / organize an IMM lipid-protein microdomain" has no adequate GO molecular
function term, so a structural subunit reads as MF-dark.
How the SAME depletion produces OPPOSITE ageing outcomes (life-shortening in WT
vs life-extending in daf-2 / DR / mitochondrial mutants) is mechanistically
unexplained — the metabolic node the complex sits on is not defined.

Annotation-relevant reasoning

The 11 WB IMP annotations (PMID:12794069) and the 11 ARBA IEA annotations
(GO_REF:0000117) are pairwise redundant on the same term set (regulation of
oxidative phosphorylation, response to oxidative stress, mitochondrion
organization, spermatogenesis, gonad development, embryo development, defecation,
positive regulation of multicellular organism growth, regulation of nematode
pharyngeal pumping, oogenesis). The ARBA rules appear to recapitulate the C.
elegans phenotype literature. The IEA rows are redundant electronic echoes of the
experimental IMP rows.
Many of the IMP phenotype terms (defecation, pharyngeal pumping, positive
regulation of growth, spermatogenesis, oogenesis, oxidative stress response) are
downstream/pleiotropic consequences of losing an essential mitochondrial
complex, not evidence of a dedicated phb-1 role in each named process. These are
best kept as NON-core (pleiotropy of an essential mito gene) rather than as core
functions. The abstract of PMID:12794069 supports embryonic + germline/gonad +
mitochondrial biogenesis phenotypes directly; the more specific behavioural terms
(defecation, pharyngeal pumping) are in the full text, which curators read — do
not REMOVE, keep as non-core.
Core: complex membership (GO:0035632), IMM localization (GO:0005743),
mitochondrion organization (GO:0007005), protein stabilization (GO:0050821 —
complex-level chaperone role). Structural-subunit MF ≈ structural molecule
activity (GO:0005198); the complex's true activity is the ontology/biology gap.

Provenance / sources

PMID:12794069 — Artal-Sanz et al. 2003, J Biol Chem (RNAi phenotype; complex; IMM).
Abstract-only in cache; curators (WB) read full text for the IMP/IDA rows.
PMID:19812672 — Artal-Sanz & Tavernarakis 2009, Nature (longevity/diapause/fat).
Abstract-only in cache. Source of IPI complex annotation (with phb-2).
PMID:26092086 — Lourenço et al. 2015, BBA Bioenergetics (metabolome; full text in
cache). Source of ComplexPortal IDA/NAS rows; richest verbatim source.
UniProt Q9BKU4; PANTHER PTHR23222; ComplexPortal CPX-4114.

Falcon deep-research synthesis (phb-1-deep-research-falcon.md, 33 citations)

The falcon report (Edison Scientific; genuine, 20-min run) reinforces and enriches
the picture above. Additional mechanistic context (grounded in review/primary
literature cited there; not all in our cached PMIDs, so used as context only, not as
verbatim supporting_text in the YAML):

Membrane-bound scaffold + holdase/chaperone: "PHB-1 is not an enzyme,
transporter, or signaling receptor. Rather, it functions as a membrane-bound
scaffold and holdase/unfoldase-type chaperone within the inner mitochondrial
membrane" and "Its precise biochemical activity has remained challenging to
define" — direct confirmation of the MF-dark ontology/biology gap I recorded.
m-AAA protease / OPA1 / cristae: the complex physically interacts with the
m-AAA proteases (SPG-7/paraplegin; AFG3L2) and restrains OMA1, stabilizing long
OPA1 (worm EAT-3) isoforms; loss → aberrant OPA1 processing, cristae disruption,
mitochondrial fragmentation (matches the "altered mitochondrial biogenesis"
phenotype in Artal-Sanz 2003). [Hernando-Rodríguez & Artal-Sanz 2018, Cells;
DOI 10.3390/cells7120238]
Lipid organization: interacts with cardiolipin / phosphatidylethanolamine
metabolism; the SPFH domain may bind lipids (not biochemically proven) — one arm
of the scaffold-vs-chaperone-vs-lipid-organizer debate.
Nucleoid / mtDNA: associates with nucleoids (with ATAD3/TFAM); depletion
reduces mitochondrial protein synthesis.
Mitophagy is via PHB-2, not phb-1 directly: PHB-2 is the IMM LC3 receptor
(LIR motif); phb-1 participates only through the heterocomplex. This is why
phb-1 appears in the CAEEL_MITOPHAGY flagship (as part of import/proteostasis).
[Wei et al. 2017, Cell]
Context-dependent longevity mechanism (the second knowledge gap): PHB
depletion shortens WT lifespan but extends it in daf-2 (IIS), sgk-1 and rict-1
(TORC2) mutants and under dietary restriction; SGK-1 is a major determinant;
requires UPRmt + autophagy (not mitophagy) and SREBP/SBP-1; strongly induces
UPRmt via ATFS-1. [Gatsi 2014 PLoS ONE 10.1371/journal.pone.0107671;
de la Cruz-Ruiz 2021 Aging Cell 10.1111/acel.13359; Lourenço & Artal-Sanz 2021
Metabolites 10.3390/metabo11090636]
2025 in situ structure: cryo-ET resolved the human PHB complex as a
bell-shaped 11-subunit alternating PHB1/PHB2 assembly (~190 Å), refining the
older "12–16 heterodimer ~1 MDa ring" model; worm stoichiometry not independently
resolved. [Lange et al. 2025, Nat Cell Biol 10.1038/s41556-025-01620-1]

None of these change the GOA annotation actions; they corroborate keeping the
complex/localization/mito-organization/protein-stabilization terms as core and the
developmental/behavioural terms as pleiotropic non-core, and they sharpen the two
recorded knowledge gaps (mechanism; opposite-longevity node).

📄 View Raw YAML

id: Q9BKU4
gene_symbol: phb-1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:6239
  label: Caenorhabditis elegans
description: >-
  phb-1 encodes prohibitin-1, one of the two subunits (with phb-2) of the
  mitochondrial prohibitin (PHB) complex, a ring-shaped, high-molecular-weight
  assembly embedded in the inner mitochondrial membrane. PHB-1 and PHB-2 are
  mutually dependent: they bind each other to form heterodimers that oligomerize
  into the ring, and loss of either subunit destabilizes the entire complex. The
  protein belongs to the SPFH/Band-7 (stomatin/prohibitin) superfamily. The
  complex is proposed to act as a membrane-bound chaperone that holds and
  stabilizes newly synthesized mitochondrial-encoded respiratory-chain proteins
  and/or as a scaffold that organizes inner-membrane proteins within a defined
  lipid environment. In C. elegans the complex is essential: depletion of phb-1
  blocks embryonic development, disrupts somatic and germline differentiation of
  the gonad, and alters mitochondrial biogenesis in body-wall muscle. Beyond this
  essential developmental role, the prohibitin complex is a context-dependent
  modulator of ageing that couples mitochondrial metabolism and fat utilization to
  insulin/IGF (daf-2) and dietary-restriction signalling: its depletion shortens
  the lifespan of otherwise wild-type animals but extends the lifespan of diapause,
  dietary-restricted, and respiration- or fat-metabolism-compromised animals.
existing_annotations:
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Correct but general mitochondrial localization inferred phylogenetically.
      The more specific inner-membrane and prohibitin-complex localizations are
      experimentally supported and separately annotated, so this broad term is
      retained as non-core.
    action: KEEP_AS_NON_CORE
    reason: >-
      phb-1 is a bona fide mitochondrial protein, so the term is not wrong, but
      GO:0005743 (mitochondrial inner membrane) and GO:0035632 (mitochondrial
      prohibitin complex) are the informative, experimentally supported
      localizations for this subunit.
- term:
    id: GO:0007005
    label: mitochondrion organization
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      Phylogenetic inference that phb-1 acts in mitochondrion organization,
      corroborated by experimental (IMP) and author-statement (NAS) annotations
      for the same term. A core process for this gene.
    action: ACCEPT
    reason: >-
      Consistent with the experimentally demonstrated requirement of the PHB
      complex for normal mitochondrial biogenesis/organization.
    supported_by:
    - reference_id: PMID:12794069
      supporting_text: >-
        a deficiency in PHB proteins results in altered mitochondrial biogenesis
        in body wall muscle cells
      reference_section_type: ABSTRACT
- term:
    id: GO:0002082
    label: regulation of oxidative phosphorylation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >-
      Electronic (ARBA) annotation that mirrors the experimental WB IMP annotation
      to the same term. Biologically defensible given the conserved role of
      prohibitins in stabilizing respiratory-chain subunits, but it is a downstream
      consequence of complex loss rather than a dedicated phb-1 activity.
    action: KEEP_AS_NON_CORE
    reason: >-
      Redundant electronic echo of the experimental IMP annotation (PMID:12794069);
      effect on oxidative phosphorylation is an indirect consequence of losing an
      essential inner-membrane complex, so it is non-core.
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Electronic subcellular-location mapping to the mitochondrial inner membrane,
      independently confirmed by experimental IDA evidence. This is the correct,
      core localization of the PHB complex.
    action: ACCEPT
    reason: >-
      The inner-membrane localization is experimentally established (see the
      ComplexPortal IDA annotation) and matches the UniProt SUBCELLULAR LOCATION.
    supported_by:
    - reference_id: PMID:12794069
      supporting_text: >-
        prohibitins in C. elegans form a high molecular weight complex in the
        mitochondrial inner membrane similar to that of yeast and humans
      reference_section_type: ABSTRACT
- term:
    id: GO:0006979
    label: response to oxidative stress
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >-
      Electronic (ARBA) annotation mirroring the WB IMP annotation. Altered
      oxidative-stress sensitivity is a plausible but indirect consequence of
      impaired mitochondrial function in prohibitin-depleted animals.
    action: KEEP_AS_NON_CORE
    reason: >-
      Redundant with the experimental IMP annotation (PMID:12794069); pleiotropic
      downstream phenotype of an essential mitochondrial gene, not a core function.
- term:
    id: GO:0007283
    label: spermatogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >-
      Electronic (ARBA) annotation mirroring the WB IMP germline phenotype.
    action: KEEP_AS_NON_CORE
    reason: >-
      Redundant with the experimental IMP annotation (PMID:12794069); germline/
      spermatogenesis defects are a pleiotropic consequence of depleting an
      essential mitochondrial complex, not a dedicated phb-1 function.
- term:
    id: GO:0008406
    label: gonad development
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >-
      Electronic (ARBA) annotation mirroring the WB IMP gonad phenotype.
    action: KEEP_AS_NON_CORE
    reason: >-
      Redundant with the experimental IMP annotation (PMID:12794069); pleiotropic
      developmental consequence of losing the essential PHB complex.
- term:
    id: GO:0009792
    label: embryo development ending in birth or egg hatching
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >-
      Electronic (ARBA) annotation mirroring the WB IMP embryonic-lethality
      phenotype.
    action: KEEP_AS_NON_CORE
    reason: >-
      Redundant with the experimental IMP annotation (PMID:12794069); embryonic
      arrest reflects the essentiality of the complex rather than a dedicated
      embryogenesis function of phb-1.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: located_in
  review:
    summary: >-
      Generic InterPro-to-GO membrane localization. Uninformative given that the
      specific mitochondrial inner-membrane localization is experimentally
      established.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      GO:0016020 (membrane) is an over-general parent; the informative and correct
      localization GO:0005743 (mitochondrial inner membrane) is already annotated.
- term:
    id: GO:0030421
    label: defecation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >-
      Electronic (ARBA) annotation mirroring the WB IMP behavioural phenotype.
    action: KEEP_AS_NON_CORE
    reason: >-
      Redundant with the experimental IMP annotation (PMID:12794069); altered
      defecation is a pleiotropic behavioural consequence of mitochondrial
      dysfunction, not a core molecular role.
- term:
    id: GO:0040018
    label: positive regulation of multicellular organism growth
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >-
      Electronic (ARBA) annotation mirroring the WB IMP body-size/growth
      phenotype.
    action: KEEP_AS_NON_CORE
    reason: >-
      Redundant with the experimental IMP annotation (PMID:12794069); reduced
      growth on prohibitin depletion is a systemic consequence of impaired
      mitochondrial function, not a dedicated function.
- term:
    id: GO:0043051
    label: regulation of nematode pharyngeal pumping
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >-
      Electronic (ARBA) annotation mirroring the WB IMP behavioural phenotype.
    action: KEEP_AS_NON_CORE
    reason: >-
      Redundant with the experimental IMP annotation (PMID:12794069); pharyngeal
      pumping change is a pleiotropic behavioural consequence, not a core function.
- term:
    id: GO:0048477
    label: oogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >-
      Electronic (ARBA) annotation mirroring the WB IMP germline phenotype.
    action: KEEP_AS_NON_CORE
    reason: >-
      Redundant with the experimental IMP annotation (PMID:12794069); oogenesis
      defects are a pleiotropic consequence of losing the essential PHB complex.
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: IDA
  original_reference_id: PMID:26092086
  qualifier: located_in
  review:
    summary: >-
      Direct experimental evidence (ComplexPortal curation) that the PHB complex,
      of which phb-1 is a subunit, resides in the mitochondrial inner membrane.
      Core localization.
    action: ACCEPT
    reason: >-
      Established inner-membrane localization; the heterodimer assembles into a
      ring embedded in the inner mitochondrial membrane.
    supported_by:
    - reference_id: PMID:26092086
      supporting_text: >-
        which bind to each other to form a heterodimer that is assembled into a
        ring-like macromolecular structure at the inner mitochondrial membrane
      reference_section_type: INTRODUCTION
- term:
    id: GO:0007005
    label: mitochondrion organization
  evidence_type: NAS
  original_reference_id: PMID:26092086
  qualifier: involved_in
  review:
    summary: >-
      Author-stated involvement of the PHB complex in mitochondrion organization,
      consistent with the experimental IMP annotation. Core process.
    action: ACCEPT
    reason: >-
      Prohibitin depletion perturbs mitochondrial biogenesis/organization; a
      well-supported core role.
    supported_by:
    - reference_id: PMID:12794069
      supporting_text: >-
        a deficiency in PHB proteins results in altered mitochondrial biogenesis
        in body wall muscle cells
      reference_section_type: ABSTRACT
- term:
    id: GO:0035632
    label: mitochondrial prohibitin complex
  evidence_type: IDA
  original_reference_id: PMID:26092086
  qualifier: part_of
  review:
    summary: >-
      Direct evidence that phb-1 is part of the mitochondrial prohibitin complex.
      This complex membership is the defining, primary core annotation for phb-1.
    action: ACCEPT
    reason: >-
      phb-1 and phb-2 form the obligate ring complex; membership is experimentally
      established and the two subunits are interdependent for its formation.
    supported_by:
    - reference_id: PMID:26092086
      supporting_text: >-
        These two subunits are interdependent for the formation of the complex,
        leading the absence of one of them to the absence of the whole complex
      reference_section_type: INTRODUCTION
- term:
    id: GO:0050821
    label: protein stabilization
  evidence_type: NAS
  original_reference_id: PMID:26092086
  qualifier: involved_in
  review:
    summary: >-
      Author-stated role of the PHB complex as a membrane-bound chaperone that
      holds and stabilizes newly synthesized mitochondrial-encoded proteins. This
      is the closest capture of the complex's candidate molecular role, though it
      is a proposed (largely yeast/human-derived) function rather than one
      biochemically demonstrated in worm.
    action: ACCEPT
    reason: >-
      Represents the proposed complex-level chaperone/holdase activity; retained
      as a candidate core function, with the caveat that the true molecular
      mechanism remains debated (see knowledge_gaps).
    supported_by:
    - reference_id: PMID:26092086
      supporting_text: >-
        a membrane-bound chaperone, which holds and stabilizes newly synthesised
        mitochondrial-encoded proteins
      reference_section_type: INTRODUCTION
- term:
    id: GO:0035632
    label: mitochondrial prohibitin complex
  evidence_type: IPI
  original_reference_id: PMID:19812672
  qualifier: part_of
  review:
    summary: >-
      Physical-interaction evidence (with phb-2, WB:WBGene00004015) that phb-1 is
      part of the mitochondrial prohibitin complex. Direct support for the obligate
      phb-1/phb-2 partnership.
    action: ACCEPT
    reason: >-
      Confirms the direct phb-1/phb-2 interaction that constitutes the ring
      complex; a defining core annotation.
    supported_by:
    - reference_id: PMID:19812672
      supporting_text: >-
        form a ring-like, high-molecular-mass complex at the inner membrane of
        mitochondria
      reference_section_type: ABSTRACT
- term:
    id: GO:0002082
    label: regulation of oxidative phosphorylation
  evidence_type: IMP
  original_reference_id: PMID:12794069
  qualifier: involved_in
  review:
    summary: >-
      Experimental (RNAi) evidence linking prohibitin depletion to altered
      oxidative phosphorylation, consistent with the conserved role of the complex
      in stabilizing respiratory-chain subunits. An indirect, non-core consequence
      of losing the essential complex.
    action: KEEP_AS_NON_CORE
    reason: >-
      Full-text-based experimental annotation (retained, not removed); effect on
      oxidative phosphorylation reflects downstream respiratory-chain destabilization
      rather than a dedicated regulatory activity of phb-1.
- term:
    id: GO:0006979
    label: response to oxidative stress
  evidence_type: IMP
  original_reference_id: PMID:12794069
  qualifier: involved_in
  review:
    summary: >-
      Experimental (RNAi) evidence of altered oxidative-stress response upon
      prohibitin depletion. Pleiotropic consequence of mitochondrial dysfunction.
    action: KEEP_AS_NON_CORE
    reason: >-
      Retained as an experimental annotation; oxidative-stress phenotype is an
      indirect consequence of impaired mitochondrial function, not a core role.
- term:
    id: GO:0007005
    label: mitochondrion organization
  evidence_type: IMP
  original_reference_id: PMID:12794069
  qualifier: involved_in
  review:
    summary: >-
      Experimental (RNAi) evidence that prohibitin depletion alters mitochondrial
      biogenesis/organization in body-wall muscle. Core process for phb-1.
    action: ACCEPT
    reason: >-
      Directly supported by the observed mitochondrial-biogenesis defect; a core
      function of the complex.
    supported_by:
    - reference_id: PMID:12794069
      supporting_text: >-
        a deficiency in PHB proteins results in altered mitochondrial biogenesis
        in body wall muscle cells
      reference_section_type: ABSTRACT
- term:
    id: GO:0007283
    label: spermatogenesis
  evidence_type: IMP
  original_reference_id: PMID:12794069
  qualifier: involved_in
  review:
    summary: >-
      Experimental (RNAi) germline phenotype. Pleiotropic developmental
      consequence of depleting the essential PHB complex.
    action: KEEP_AS_NON_CORE
    reason: >-
      Retained as an experimental annotation; germline/spermatogenesis defects
      follow from loss of an essential mitochondrial complex during germline
      differentiation rather than a dedicated spermatogenesis function.
    supported_by:
    - reference_id: PMID:12794069
      supporting_text: >-
        PHB proteins are essential during embryonic development and are required
        for somatic and germline differentiation in the larval gonad
      reference_section_type: ABSTRACT
- term:
    id: GO:0008406
    label: gonad development
  evidence_type: IMP
  original_reference_id: PMID:12794069
  qualifier: involved_in
  review:
    summary: >-
      Experimental (RNAi) evidence of somatic and germline gonad differentiation
      defects. Pleiotropic developmental consequence.
    action: KEEP_AS_NON_CORE
    reason: >-
      Retained as an experimental annotation; gonad-development defect reflects the
      essentiality of the complex in dividing/differentiating tissue, not a
      dedicated gonadogenesis function.
    supported_by:
    - reference_id: PMID:12794069
      supporting_text: >-
        PHB proteins are essential during embryonic development and are required
        for somatic and germline differentiation in the larval gonad
      reference_section_type: ABSTRACT
- term:
    id: GO:0009792
    label: embryo development ending in birth or egg hatching
  evidence_type: IMP
  original_reference_id: PMID:12794069
  qualifier: involved_in
  review:
    summary: >-
      Experimental (RNAi) embryonic-lethality phenotype. Reflects essentiality of
      the PHB complex.
    action: KEEP_AS_NON_CORE
    reason: >-
      Retained as an experimental annotation; embryonic arrest is a consequence of
      the complex being essential rather than a dedicated embryogenesis function
      of phb-1.
    supported_by:
    - reference_id: PMID:12794069
      supporting_text: >-
        PHB proteins are essential during embryonic development and are required
        for somatic and germline differentiation in the larval gonad
      reference_section_type: ABSTRACT
- term:
    id: GO:0030421
    label: defecation
  evidence_type: IMP
  original_reference_id: PMID:12794069
  qualifier: involved_in
  review:
    summary: >-
      Experimental (RNAi) behavioural phenotype scored by WormBase curators from
      the full text. Pleiotropic consequence of mitochondrial dysfunction.
    action: KEEP_AS_NON_CORE
    reason: >-
      Retained as an experimental annotation (curators read the full text); altered
      defecation is a pleiotropic behavioural readout, not a core molecular role.
- term:
    id: GO:0031966
    label: mitochondrial membrane
  evidence_type: IDA
  original_reference_id: PMID:12794069
  qualifier: located_in
  review:
    summary: >-
      Direct experimental evidence of mitochondrial-membrane localization. Correct
      but less specific than the separately annotated mitochondrial inner membrane,
      so retained as non-core.
    action: KEEP_AS_NON_CORE
    reason: >-
      The localization is correct; GO:0005743 (mitochondrial inner membrane) is the
      more precise term and is also annotated, so this broader term is retained but
      non-core.
    supported_by:
    - reference_id: PMID:12794069
      supporting_text: >-
        prohibitins in C. elegans form a high molecular weight complex in the
        mitochondrial inner membrane similar to that of yeast and humans
      reference_section_type: ABSTRACT
- term:
    id: GO:0040018
    label: positive regulation of multicellular organism growth
  evidence_type: IMP
  original_reference_id: PMID:12794069
  qualifier: involved_in
  review:
    summary: >-
      Experimental (RNAi) body-size/growth phenotype. Systemic consequence of
      impaired mitochondrial function.
    action: KEEP_AS_NON_CORE
    reason: >-
      Retained as an experimental annotation; reduced growth on depletion is a
      systemic consequence of mitochondrial dysfunction rather than a dedicated
      growth-promoting activity.
- term:
    id: GO:0043051
    label: regulation of nematode pharyngeal pumping
  evidence_type: IMP
  original_reference_id: PMID:12794069
  qualifier: involved_in
  review:
    summary: >-
      Experimental (RNAi) behavioural phenotype. Pleiotropic consequence of
      mitochondrial dysfunction.
    action: KEEP_AS_NON_CORE
    reason: >-
      Retained as an experimental annotation; pharyngeal-pumping change is a
      pleiotropic behavioural readout, not a core molecular role.
- term:
    id: GO:0048477
    label: oogenesis
  evidence_type: IMP
  original_reference_id: PMID:12794069
  qualifier: involved_in
  review:
    summary: >-
      Experimental (RNAi) germline phenotype. Pleiotropic developmental
      consequence of depleting the essential PHB complex.
    action: KEEP_AS_NON_CORE
    reason: >-
      Retained as an experimental annotation; oogenesis defects follow from loss of
      an essential mitochondrial complex during germline differentiation.
    supported_by:
    - reference_id: PMID:12794069
      supporting_text: >-
        PHB proteins are essential during embryonic development and are required
        for somatic and germline differentiation in the larval gonad
      reference_section_type: ABSTRACT
core_functions:
- description: >-
    phb-1 is a structural constituent of the mitochondrial prohibitin ring
    complex. It has no known independent catalytic activity; instead its function
    is to be an obligate subunit that, together with phb-2, assembles into the
    ring-shaped, high-molecular-weight PHB complex embedded in the mitochondrial
    inner membrane. The two subunits are interdependent, so phb-1 is required for
    the existence of the complex itself.
  molecular_function:
    id: GO:0005198
    label: structural molecule activity
  locations:
  - id: GO:0005743
    label: mitochondrial inner membrane
  in_complex:
    id: GO:0035632
    label: mitochondrial prohibitin complex
  supported_by:
  - reference_id: PMID:26092086
    supporting_text: >-
      which bind to each other to form a heterodimer that is assembled into a
      ring-like macromolecular structure at the inner mitochondrial membrane
    reference_section_type: INTRODUCTION
  - reference_id: PMID:26092086
    supporting_text: >-
      These two subunits are interdependent for the formation of the complex,
      leading the absence of one of them to the absence of the whole complex
    reference_section_type: INTRODUCTION
- description: >-
    As part of the mitochondrial prohibitin complex, phb-1 contributes to
    organization of the mitochondrial inner membrane and to stabilization of
    newly synthesized mitochondrial-encoded proteins (a proposed membrane-bound
    chaperone/scaffold role), and thereby to mitochondrial biogenesis and function.
    Through this activity the complex acts as a context-dependent modulator of
    mitochondrial metabolism, fat utilization, and adult lifespan.
  directly_involved_in:
  - id: GO:0007005
    label: mitochondrion organization
  - id: GO:0050821
    label: protein stabilization
  locations:
  - id: GO:0005743
    label: mitochondrial inner membrane
  in_complex:
    id: GO:0035632
    label: mitochondrial prohibitin complex
  supported_by:
  - reference_id: PMID:12794069
    supporting_text: >-
      a deficiency in PHB proteins results in altered mitochondrial biogenesis in
      body wall muscle cells
    reference_section_type: ABSTRACT
  - reference_id: PMID:26092086
    supporting_text: >-
      a membrane-bound chaperone, which holds and stabilizes newly synthesised
      mitochondrial-encoded proteins
    reference_section_type: INTRODUCTION
  - reference_id: PMID:19812672
    supporting_text: >-
      the mitochondrial prohibitin complex promotes longevity by modulating
      mitochondrial function and fat metabolism
    reference_section_type: ABSTRACT
knowledge_gaps:
- gap_statement: >-
    The molecular mechanism of the mitochondrial prohibitin complex is
    unresolved. It is not established whether the complex acts primarily as a
    membrane-bound chaperone/holdase for newly synthesized mitochondrial-encoded
    proteins, as a scaffold that organizes inner-membrane proteins within a
    defined (cardiolipin/phospholipid) microdomain, or as a regulator of
    inner-membrane proteostasis (e.g. of the m-AAA protease); nor is the direct
    molecular activity of phb-1 as a ring subunit expressible as a specific GO
    molecular function.
  boundary: >-
    It is firmly established that phb-1 and phb-2 bind each other and assemble into
    a ring-like, high-molecular-weight complex in the mitochondrial inner membrane,
    that the two subunits are interdependent (loss of one abolishes the complex),
    and that depletion is embryonic-lethal, disrupts gonad/germline differentiation,
    alters mitochondrial biogenesis, and context-dependently modulates lifespan.
    What is NOT established is the biochemical mechanism by which the complex
    produces these effects.
  gap_kind:
  - BIOLOGY
  - ONTOLOGY
  dark_aspect: MF_DARK
  status: OPEN
  significance: >-
    Prohibitins are ubiquitous and essential across eukaryotes; resolving whether
    the complex is fundamentally a chaperone, a membrane scaffold, or a lipid/
    proteostasis organizer would explain a large body of pleiotropic phenotypes and
    the conserved link between mitochondrial membrane organization and ageing. The
    absence of a GO molecular-function term for a structural ring subunit is why the
    gene reads as MF-dark despite rich process/localization annotation.
  resolution: >-
    In vitro reconstitution / structural work on the worm (or conserved) PHB ring to
    test holdase vs scaffold activity; lipidomic and proximity-labeling mapping of
    the inner-membrane microdomain the complex organizes; separation-of-function
    alleles that uncouple candidate activities. In parallel, an ontology term for
    the structural/scaffolding molecular activity of a prohibitin-type ring subunit.
  provenance:
  - reference_id: PMID:26092086
    supporting_text: >-
      the true function of the mitochondrial prohibitin complex remains elusive
    reference_section_type: ABSTRACT
  - reference_id: PMID:26092086
    supporting_text: >-
      as scaffold proteins that recruit membrane proteins to a specific lipid
      environment
    reference_section_type: INTRODUCTION
  proposed_terms:
  - proposed_name: prohibitin complex structural constituent activity
    proposed_definition: >-
      A structural molecule activity of a prohibitin-family (SPFH/Band-7) protein by
      which it acts as an obligate subunit of the ring-shaped mitochondrial
      prohibitin complex, contributing to the assembly and integrity of a
      membrane-bound scaffold/holdase in the inner mitochondrial membrane, without
      itself catalyzing a known biochemical reaction.
    justification: >-
      phb-1/phb-2 and their orthologs have no adequate GO molecular-function term
      for their role as structural ring subunits and inner-membrane scaffolds. They
      are currently annotatable only at the complex/process level or with the
      generic 'structural molecule activity', leaving the gene MF-dark despite a
      well-defined cellular role.
    proposed_parent:
      id: GO:0005198
      label: structural molecule activity
- gap_statement: >-
    The mechanistic basis by which the SAME reduction of the prohibitin complex
    produces OPPOSITE ageing outcomes is unknown - prohibitin deficiency shortens
    the lifespan of otherwise wild-type animals yet extends the lifespan of
    diapause (daf-2), dietary-restricted, and respiration/fat-metabolism-compromised
    animals. The metabolic node at which the complex converts genetic/nutritional
    context into opposite longevity responses is undefined.
  boundary: >-
    The context-dependence itself is well documented (life-shortening in wild type
    vs life-extending in daf-2/DR/mitochondrial mutants), and depletion is known to
    change ATP levels, fat content, mitochondrial proliferation, and the whole-animal
    metabolome. The upstream signalling (insulin/IGF-DAF-16, dietary restriction) and
    the downstream metabolic readouts are mapped, but the causal molecular link
    through the complex is not.
  gap_kind:
  - BIOLOGY
  dark_aspect: RESIDUAL_SUBGAP
  status: OPEN
  significance: >-
    This paradox is a clean, conserved example of how mitochondrial membrane
    organization gates lifespan in a metabolic-state-dependent manner; resolving it
    would connect prohibitin biology to insulin/IGF and dietary-restriction ageing
    pathways mechanistically.
  resolution: >-
    Epistasis and metabolic-flux analysis across the opposing backgrounds; identify
    the prohibitin-dependent metabolic step whose perturbation flips the longevity
    sign; test candidate mediators (fat mobilization, respiratory-chain assembly).
  provenance:
  - reference_id: PMID:19812672
    supporting_text: >-
      knockdown of prohibitin promotes longevity in diapause mutants or under
      conditions of dietary restriction
    reference_section_type: ABSTRACT
  - reference_id: PMID:26092086
    supporting_text: >-
      while it dramatically extends the lifespan of the already long-lived
      daf-2(e1370) insulin receptor mutants
    reference_section_type: INTRODUCTION
suggested_questions:
- question: >-
    Is the worm PHB complex primarily a chaperone/holdase for nascent
    mitochondrial-encoded proteins, a membrane/lipid scaffold, or a regulator of
    inner-membrane proteostasis?
- question: >-
    What is the direct molecular partnership between the PHB ring and the m-AAA
    protease (SPG-7/paraplegin) in C. elegans, and does it explain any of the
    depletion phenotypes?
- question: >-
    Which prohibitin-dependent metabolic step determines whether depletion shortens
    or extends lifespan in a given genetic/nutritional context?
suggested_experiments:
- description: >-
    Reconstitute or affinity-purify the worm PHB ring and test in vitro holdase/
    chaperone activity against candidate mitochondrial-encoded substrates versus a
    scaffold/lipid-organizing readout, to discriminate the proposed molecular roles.
  experiment_type: biochemical reconstitution
- description: >-
    Perform proximity-labeling (BioID/TurboID) and lipidomics on tagged phb-1 to map
    the inner-membrane protein/lipid microdomain organized by the complex.
  experiment_type: proximity proteomics / lipidomics
- description: >-
    Carry out epistasis and targeted metabolic-flux analysis of phb-1 depletion
    across wild-type, daf-2, and dietary-restricted backgrounds to localize the node
    responsible for the opposite longevity outcomes.
  experiment_type: genetic epistasis / metabolomics
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: PMID:12794069
  title: The mitochondrial prohibitin complex is essential for embryonic viability
    and germline function in Caenorhabditis elegans.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified primary paper (Artal-Sanz et al. 2003, J Biol Chem). Source of
      the WormBase experimental (IMP/IDA) annotations. The abstract directly supports
      inner-membrane high-molecular-weight complex formation, embryonic essentiality,
      germline/somatic gonad differentiation defects, and altered mitochondrial
      biogenesis; the more specific behavioural terms (defecation, pharyngeal pumping)
      derive from the full text read by curators.
- id: PMID:19812672
  title: Prohibitin couples diapause signalling to mitochondrial metabolism during
    ageing in C. elegans.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified primary paper (Artal-Sanz & Tavernarakis 2009, Nature). Source
      of the physical-interaction (IPI, with phb-2) complex annotation and of the
      context-dependent longevity role. Abstract supports the ring-like inner-membrane
      complex and the opposite lifespan outcomes in wild-type vs diapause/DR animals.
- id: PMID:26092086
  title: Analysis of the effect of the mitochondrial prohibitin complex, a context-dependent
    modulator of longevity, on the C. elegans metabolome.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified primary paper with full text in cache (Lourenço et al. 2015, BBA
      Bioenergetics). Source of the ComplexPortal IDA/NAS annotations and the richest
      verbatim source for complex architecture (heterodimeric ring, subunit
      interdependence), the proposed chaperone/scaffold molecular roles, and the
      explicit statement that the true function of the complex remains elusive.

phb-1

Gene Description

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

Knowledge Gaps

Deep Research

Falcon

Comprehensive Research Report: phb-1 (Prohibitin-1) in Caenorhabditis elegans

1. Gene Identity and Protein Overview

2. Structure and Complex Formation

3. Subcellular Localization

4. Primary Molecular Function

4.1. Membrane Protein Quality Control and OXPHOS Complex Assembly

4.2. Cristae Morphogenesis and OPA1 Regulation

4.3. Membrane Lipid Organization

4.4. Mitochondrial Nucleoid Organization and mtDNA Maintenance

4.5. Mitophagy (via PHB-2)

5. Biological Processes and Signaling Pathways

5.1. Essential Role in Development and Germline Function

5.2. Context-Dependent Modulation of Lifespan

5.3. Insulin/IGF-1 Signaling (IIS) Pathway

5.4. TORC2/SGK-1 Signaling

5.5. Mitochondrial Unfolded Protein Response (UPRmt)

5.6. Fat Metabolism and Metabolic Reprogramming

6. Evolutionary Conservation and Structural Insights

7. Summary

Artifacts

Citations

📚 Additional Documentation

Notes

phb-1 (Caenorhabditis elegans) — research notes

One-line summary

KNOWN (well supported)

NOT known / debated (knowledge gaps)

Annotation-relevant reasoning

Provenance / sources

Falcon deep-research synthesis (phb-1-deep-research-falcon.md, 33 citations)

📄 View Raw YAML