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.
| 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 |
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Download this section (compressed HTML)Q: 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?
Q: 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?
Q: Which prohibitin-dependent metabolic step determines whether depletion shortens or extends lifespan in a given genetic/nutritional context?
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
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):
Proposed term (ontology gap):
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):
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