Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0003924 GTPase activity	IBA GO_REF:0000033	ACCEPT	Summary: DRP-1 is a dynamin-related GTPase with conserved GTPase domains. The protein contains a Dynamin-type G domain (aa 24-304) with G1-G5 motifs characteristic of GTPases. Mutations in conserved GTPase domain residues (K40A, V43F, T61A) cause disrupted mitochondrial morphology (PMID:10619028), indicating GTPase activity is essential for function. Cross-species biochemical studies confirm Drp1 GTPase activity is assembly-stimulated and required for membrane scission. Reason: Core molecular function supported by domain architecture and mutational analysis. The K40A mutation in the GTPase domain causes 80% of cells to have irregular mitochondria (PMID:10619028). IBA annotation is appropriate given strong phylogenetic conservation of this function in the dynamin superfamily. Supporting Evidence: PMID:10619028 Mutant DRP-1 causes the mitochondrial matrix to retract into large blebs that are both surrounded and connected by tubules of outer membrane.
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: DRP-1 localizes to the cytosol and is recruited to mitochondria at fission sites. UniProt annotation confirms cytosol localization with experimental evidence (PMID:21949250). Reason: Consistent with cytosolic localization before recruitment to mitochondrial membrane. DRP-1 exists in cytosolic pools and is recruited to mitochondria upon fission signals, which is a general feature of dynamin-related proteins. Supporting Evidence: PMID:21949250 the EGL-1-CED-9 complex promotes mitochondrial fission by recruiting DRP-1 to mitochondria
GO:0016020 membrane	IBA GO_REF:0000033	ACCEPT	Summary: DRP-1 associates with membranes, specifically the mitochondrial outer membrane where it mediates fission. The term 'membrane' is very general. Reason: DRP-1 does associate with membranes (mitochondrial outer membrane specifically). While more specific terms exist, this IBA annotation captures a broad but accurate property of the protein. The more specific annotation to mitochondrial outer membrane is also present. Supporting Evidence: PMID:10619028 DRP-1 fused to GFP is observed in spots on mitochondria where scission eventually occurs.
GO:0000266 mitochondrial fission	IBA GO_REF:0000033	ACCEPT	Summary: Mitochondrial fission is the core biological process function of DRP-1. Multiple experimental studies demonstrate DRP-1 is required for mitochondrial outer membrane scission (PMID:10619028, PMID:19327994, PMID:18827010). Reason: This is the primary, defining function of DRP-1. Loss of DRP-1 function causes inhibition of mitochondrial outer membrane scission, while overexpression causes excessive fragmentation (PMID:10619028). This function is well-conserved across eukaryotes in the dynamin-related protein family. Supporting Evidence: PMID:10619028 wild-type DRP-1 contributes to the final stages of mitochondrial division by controlling scission of the mitochondrial outer membrane.
GO:0048312 intracellular distribution of mitochondria	IBA GO_REF:0000033	ACCEPT	Summary: DRP-1 mutants show abnormal mitochondrial distribution. The fission function of DRP-1 contributes to proper mitochondrial inheritance and distribution. UniProt notes disruption phenotype includes disorganized gonads with abnormal mitochondrial distribution (PMID:10619028). Reason: The annotation is appropriate as mitochondrial fission is necessary for proper distribution of mitochondria during cell division and within cells. Loss of drp-1 causes disorganized gonads with abnormal mitochondrial distribution. Supporting Evidence: PMID:10619028 mitochondria are disrupted by mutations in a C. elegans dynamin-related protein (DRP-1).
GO:0016559 peroxisome fission	IBA GO_REF:0000033	ACCEPT	Summary: Peroxisome fission function is inferred by similarity to mammalian DRP1/DNM1L which is well-documented to mediate peroxisome fission. UniProt annotates this function with ISS evidence (ECO:0000250\|UniProtKB:O00429). Reason: Mammalian DRP1 is established to mediate both mitochondrial and peroxisomal fission using the same membrane scission mechanism. The IBA annotation is phylogenetically sound given the conservation of this dual function in the Drp1 family. No direct experimental evidence in C. elegans, but strong inference from ortholog function. Supporting Evidence: file:worm/drp-1/drp-1-deep-research-falcon.md DRP-1 catalyzes mitochondrial (and peroxisomal, by inference) fission by binding the outer mitochondrial membrane (OMM), oligomerizing, and coupling GTP hydrolysis to membrane constriction and scission
GO:0005739 mitochondrion	IBA GO_REF:0000033	ACCEPT	Summary: DRP-1 localizes to mitochondria at fission sites. DRP-1::GFP is observed in spots on mitochondria where scission occurs (PMID:10619028). Reason: Well-supported by experimental evidence. DRP-1 is recruited to mitochondria to execute its fission function. Supporting Evidence: PMID:10619028 DRP-1 fused to GFP is observed in spots on mitochondria where scission eventually occurs.
GO:0005874 microtubule	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: This annotation appears to be inherited from classical dynamin family members that associate with microtubules for endocytic vesicle transport. While dynamin superfamily members can associate with microtubules, there is no direct evidence for DRP-1 microtubule localization in C. elegans. Reason: This annotation likely derives from phylogenetic inference across the broader dynamin family, but DRP-1/Drp1 subfamily proteins function at mitochondria and peroxisomes, not at the plasma membrane or in endocytic trafficking where microtubule association is relevant. No C. elegans-specific evidence supports this localization for drp-1.
GO:0008017 microtubule binding	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: Similar to the microtubule localization annotation, this molecular function annotation appears to derive from classical dynamins rather than the DRP1 subfamily. There is no evidence that DRP-1 binds microtubules in C. elegans. Reason: The DRP-1/Drp1 subfamily is functionally distinct from classical dynamins that operate in endocytosis and require microtubule binding. DRP-1's function at mitochondria and peroxisomes does not require microtubule binding. This annotation represents over-inference from the broader dynamin family.
GO:0000166 nucleotide binding	IEA GO_REF:0000043	ACCEPT	Summary: DRP-1 binds GTP as part of its GTPase activity. The protein has conserved G1-G5 motifs for nucleotide binding in its dynamin-type G domain. Reason: This is a parent term of the more specific GTP binding annotation. While somewhat redundant given the GTP binding annotation, it is not incorrect. The IEA annotation from UniProt keyword mapping is appropriate.
GO:0003924 GTPase activity	IEA GO_REF:0000002	ACCEPT	Summary: GTPase activity is the core catalytic function. This IEA annotation from InterPro domain mapping is consistent with the IBA annotation. Reason: Duplicates the IBA annotation but via a different evidence pathway (InterPro domain mapping). Both are valid and consistent.
GO:0005525 GTP binding	IEA GO_REF:0000120	ACCEPT	Summary: GTP binding is required for DRP-1 GTPase activity and membrane fission function. The G1-G5 motifs in the dynamin-type G domain mediate GTP binding. Reason: Well-supported by domain architecture. GTP binding is an intrinsic property of the conserved dynamin GTPase domain.
GO:0005737 cytoplasm	IEA GO_REF:0000117	ACCEPT	Summary: Cytoplasmic localization is consistent with experimental evidence showing DRP-1 in cytosol before recruitment to mitochondria. Reason: Consistent with experimental observations. DRP-1 exists in cytosolic pools.
GO:0005739 mitochondrion	IEA GO_REF:0000044	ACCEPT	Summary: Mitochondrial localization is well-supported by experimental evidence showing DRP-1::GFP at mitochondrial fission sites (PMID:10619028). Reason: Consistent with experimental evidence for DRP-1 localization to mitochondria.
GO:0005741 mitochondrial outer membrane	IEA GO_REF:0000044	ACCEPT	Summary: DRP-1 functions at the mitochondrial outer membrane where it mediates membrane scission. The protein is recruited to the OMM at constriction sites. Reason: Well-supported by experimental evidence. DRP-1 controls scission of the mitochondrial outer membrane specifically (PMID:10619028). Supporting Evidence: PMID:10619028 wild-type DRP-1 contributes to the final stages of mitochondrial division by controlling scission of the mitochondrial outer membrane.
GO:0005829 cytosol	IEA GO_REF:0000044	ACCEPT	Summary: DRP-1 resides in the cytosol and is recruited to mitochondria upon fission signals. UniProt subcellular location annotation supports cytosol localization. Reason: Consistent with experimental evidence that DRP-1 exists in cytosolic pools before recruitment to mitochondria (PMID:21949250).
GO:0006915 apoptotic process	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: DRP-1 has a role in apoptosis, promoting mitochondrial fragmentation and elimination during cell death. However, drp-1 is not required for apoptosis activation but acts downstream of caspase CED-3 in cell death execution (PMID:18722182). Reason: The apoptotic role is real but secondary to the core mitochondrial fission function. DRP-1 acts downstream of CED-3 to promote mitochondrial elimination in dying cells, but is not essential for apoptosis activation. The annotation is appropriate but represents a context-dependent function rather than core function. Supporting Evidence: PMID:18722182 drp-1 and fis-2 function independent of one another and the Bcl-2 homolog CED-9 and downstream of the CED-3 caspase to promote elimination of mitochondria in dying cells
GO:0008289 lipid binding	IEA GO_REF:0000043	ACCEPT	Summary: Dynamin-related proteins bind membrane lipids as part of their membrane remodeling function. The annotation is based on UniProt lipid-binding keyword. Reason: Membrane binding is required for DRP-1 function. GTPase activity is increased by binding to phospholipid membranes (UniProt activity regulation note). Cross-species studies show Drp1 binds membranes via adaptors and lipid interactions.
GO:0016787 hydrolase activity	IEA GO_REF:0000043	ACCEPT	Summary: DRP-1 is a GTPase that hydrolyzes GTP to GDP + Pi. Hydrolase activity is a parent term of GTPase activity. Reason: True but very general. GTPase activity is a more informative child term that is also annotated. This parent term is not wrong.
GO:0000266 mitochondrial fission	IMP PMID:19327994 Bcl-2 proteins EGL-1 and CED-9 do not regulate mitochondrial...	ACCEPT	Summary: This study examined drp-1 mutants and found mitochondrial fission is defective. The study specifically looked at mitochondrial morphology in drp-1 mutants in the context of analyzing Bcl-2 protein function. Reason: Direct experimental evidence. The study confirms drp-1 mutants have defective mitochondrial fission while fusion still occurs, resulting in abnormal mitochondrial connectivity. Supporting Evidence: PMID:19327994 in a drp-1 mutant, in which mitochondrial fusion occurs but mitochondrial fission is defective
GO:0000266 mitochondrial fission	IGI PMID:18827010 CED-9 and mitochondrial homeostasis in C. elegans muscle.	ACCEPT	Summary: This study showed genetic interaction between drp-1 and ced-9 in regulating mitochondrial morphology. Increased DRP-1 expression suppresses the interconnected mitochondria phenotype caused by CED-9 overexpression. Reason: Valid genetic interaction evidence. The study demonstrates DRP-1 functions in opposition to CED-9 in controlling mitochondrial morphology, with DRP-1 promoting fission. Supporting Evidence: PMID:18827010 This mitochondrial phenotype is partially suppressed by increased expression of the dynamin-related GTPase DRP-1
GO:0000266 mitochondrial fission	IMP PMID:18827010 CED-9 and mitochondrial homeostasis in C. elegans muscle.	ACCEPT	Summary: The study examines drp-1 function in mitochondrial dynamics and shows it promotes fission. DRP-1 overexpression causes fragmented mitochondria. Reason: Direct mutant phenotype evidence supporting DRP-1 role in mitochondrial fission. Supporting Evidence: PMID:18827010 This mitochondrial phenotype is partially suppressed by increased expression of the dynamin-related GTPase DRP-1
GO:0009792 embryo development ending in birth or egg hatching	IMP PMID:10619028 C. elegans dynamin-related protein DRP-1 controls severing o...	KEEP AS NON CORE	Summary: RNAi knockdown of drp-1 causes embryonic lethality. This represents a broad developmental phenotype resulting from the essential mitochondrial fission function. Reason: The embryonic lethality phenotype is real but represents a pleiotropic consequence of disrupted mitochondrial dynamics rather than a specific developmental function. DRP-1's role is in mitochondrial fission; the developmental phenotype is downstream of this core function. Supporting Evidence: PMID:10619028 mitochondria are disrupted by mutations in a C. elegans dynamin-related protein (DRP-1).
GO:0006915 apoptotic process	IGI PMID:18722182 Caenorhabditis elegans drp-1 and fis-2 regulate distinct cel...	KEEP AS NON CORE	Summary: This study demonstrated genetic interaction between drp-1 and ced-3 (caspase) in apoptosis. DRP-1 functions downstream of CED-3 to promote cell death execution through mitochondrial elimination. Reason: The apoptotic role is real but represents a secondary function. DRP-1 is not required for apoptosis activation but acts downstream of caspase to facilitate mitochondrial elimination in dying cells. The annotation is correct but this is not the core function. Supporting Evidence: PMID:18722182 drp-1 and fis-2 function independent of one another and the Bcl-2 homolog CED-9 and downstream of the CED-3 caspase to promote elimination of mitochondria in dying cells
GO:0000266 mitochondrial fission	IMP PMID:10619028 C. elegans dynamin-related protein DRP-1 controls severing o...	ACCEPT	Summary: This is the foundational paper establishing DRP-1 function in mitochondrial fission. Mutant DRP-1 causes mitochondrial matrix to retract into blebs connected by outer membrane tubules, indicating outer membrane scission is inhibited. Overexpression causes excessive fragmentation. Reason: Primary experimental evidence establishing DRP-1 as a mitochondrial fission factor. This is the core function of the protein. Supporting Evidence: PMID:10619028 Mutant DRP-1 causes the mitochondrial matrix to retract into large blebs that are both surrounded and connected by tubules of outer membrane. This indicates that scission of the mitochondrial outer membrane is inhibited
GO:0005525 GTP binding	ISS PMID:10619028 C. elegans dynamin-related protein DRP-1 controls severing o...	ACCEPT	Summary: GTP binding is inferred by sequence similarity to mammalian DRP1 (UniProtKB:O00429). The conserved dynamin-type G domain with G1-G5 motifs supports this function. Reason: Valid sequence similarity-based inference. The conserved domain architecture strongly supports GTP binding function. Supporting Evidence: PMID:10619028 C. elegans dynamin-related protein (DRP-1)
GO:0005739 mitochondrion	IDA PMID:10619028 C. elegans dynamin-related protein DRP-1 controls severing o...	ACCEPT	Summary: Direct experimental evidence showing DRP-1::GFP localization to mitochondria at fission sites. Reason: Strong experimental evidence. GFP-tagged DRP-1 was observed at sites of mitochondrial scission. Supporting Evidence: PMID:10619028 DRP-1 fused to GFP is observed in spots on mitochondria where scission eventually occurs.
GO:0008637 apoptotic mitochondrial changes	IMP PMID:15716954 DRP-1-mediated mitochondrial fragmentation during EGL-1-indu...	ACCEPT	Summary: This study showed DRP-1 is required for mitochondrial fragmentation during EGL-1-induced cell death. DRP-1 overexpression is sufficient to induce mitochondrial fragmentation and cell death. Reason: Well-supported by experimental evidence. DRP-1 mediates mitochondrial fragmentation during apoptosis, which represents apoptotic mitochondrial changes. Supporting Evidence: PMID:15716954 DRP-1/dynamin-related protein, a key component of the mitochondrial fission machinery, is required and sufficient to induce mitochondrial fragmentation and programmed cell death during C. elegans development.

Core Functions

DRP-1 is a dynamin-related GTPase that controls mitochondrial outer membrane fission. It is recruited from the cytosol to the mitochondrial outer membrane at constriction sites, where it oligomerizes and uses GTP hydrolysis to drive membrane scission.

Molecular Function:

GTPase activity

Directly Involved In:

mitochondrial fission

Cellular Locations:

mitochondrial outer membrane cytosol

Supporting Evidence:

PMID:10619028
wild-type DRP-1 contributes to the final stages of mitochondrial division by controlling scission of the mitochondrial outer membrane.

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

IBA annotations based on PANTHER phylogenetic trees with characterized orthologs

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:10619028

C. elegans dynamin-related protein DRP-1 controls severing of the mitochondrial outer membrane.

Established DRP-1 as the mitochondrial fission factor in C. elegans

"wild-type DRP-1 contributes to the final stages of mitochondrial division by controlling scission of the mitochondrial outer membrane."
Mutant DRP-1 inhibits outer membrane scission while inner membrane scission still occurs

"Mutant DRP-1 causes the mitochondrial matrix to retract into large blebs that are both surrounded and connected by tubules of outer membrane."
DRP-1::GFP localizes to sites of mitochondrial scission

"DRP-1 fused to GFP is observed in spots on mitochondria where scission eventually occurs."
Overexpression causes excessive mitochondrial fragmentation

"Overexpressed wild-type DRP-1 causes mitochondria to become excessively fragmented"

PMID:15716954

DRP-1-mediated mitochondrial fragmentation during EGL-1-induced cell death in C. elegans.

DRP-1 is required and sufficient to induce mitochondrial fragmentation during apoptosis

"DRP-1/dynamin-related protein, a key component of the mitochondrial fission machinery, is required and sufficient to induce mitochondrial fragmentation and programmed cell death during C. elegans development."
Mitochondrial fragmentation is induced by EGL-1 and blocked by ced-9 mutations

"Mitochondrial fragmentation is induced by the BH3-only protein EGL-1 and can be blocked by mutations in the bcl-2-like gene ced-9"
Mitochondrial fragmentation is independent of CED-4 and CED-3

"Mitochondrial fragmentation is independent of CED-4/Apaf-1 and CED-3/caspase"

PMID:18722182

Caenorhabditis elegans drp-1 and fis-2 regulate distinct cell-death execution pathways downstream of ced-3 and independent of ced-9.

drp-1 is not required for apoptosis activation but acts downstream of CED-3

"profusion genes fzo-1 and eat-3 or the profission gene drp-1 are not required for apoptosis activation in C. elegans."
DRP-1 promotes mitochondrial elimination in dying cells

"drp-1 and fis-2 function independent of one another and the Bcl-2 homolog CED-9 and downstream of the CED-3 caspase to promote elimination of mitochondria in dying cells"
CED-3 cleaves DRP-1; this cleavage is required for pro-apoptotic but not fission function

"CED-3 can cleave DRP-1, which appears to be important for DRP-1's proapoptotic function, but not its mitochondria fission function."

PMID:18827010

CED-9 and mitochondrial homeostasis in C. elegans muscle.

CED-9 overexpression causes interconnected mitochondria

"increased CED-9 expression in these cells produces highly interconnected mitochondria."
DRP-1 overexpression suppresses CED-9-induced mitochondrial connectivity

"This mitochondrial phenotype is partially suppressed by increased expression of the dynamin-related GTPase DRP-1"

PMID:19327994

Bcl-2 proteins EGL-1 and CED-9 do not regulate mitochondrial fission or fusion in Caenorhabditis elegans.

drp-1 mutants have defective fission with normal fusion

"in a drp-1 mutant, in which mitochondrial fusion occurs but mitochondrial fission is defective"
EGL-1 and CED-9 do not regulate mitochondrial fission or fusion

"loss of egl-1 or ced-9, or overexpression of their gene products, had no apparent effect on mitochondrial connectivity or mitochondrial size."

PMID:21463460

The dynamin-related protein DRP-1 and the insulin signaling pathway cooperate to modulate Caenorhabditis elegans longevity.

PMID:21949250

A molecular switch that governs mitochondrial fusion and fission mediated by the BCL2-like protein CED-9 of Caenorhabditis elegans.

DRP-1 interacts with CED-9

"CED-9 also physically interacts with the mitochondrial fission protein DRP-1"
Interaction is enhanced by GTP rather than GDP

"this interaction can be enhanced when CED-9 is associated with the BH3-only protein EGL-1."
DRP-1 is recruited to mitochondria by CED-9/EGL-1 complex

"the EGL-1-CED-9 complex promotes mitochondrial fission by recruiting DRP-1 to mitochondria"

PMID:33734301

Autophagy facilitates mitochondrial rebuilding after acute heat stress via a DRP-1-dependent process.

file:worm/drp-1/drp-1-deep-research-falcon.md

Deep research summary for drp-1

DRP-1 is recruited from cytosol to OMM by adaptor proteins including FIS-1, FIS-2 and MFF-1/MFF-2
Loss of drp-1 in dystrophin mutants reduces TUNEL-positive muscle cells from 5.28 to 2.07 per animal
drp-1 disruption during development extends daf-2 (IIS) mutant longevity

Suggested Experiments

Experiment: Direct visualization of DRP-1 at peroxisomes to confirm peroxisome fission function

Experiment: Biochemical characterization of C. elegans DRP-1 GTPase activity and membrane binding properties

Experiment: Identification of the CED-3 cleavage products and their functional differences

📚 Additional Documentation

Deep Research Bioreason

(drp-1-deep-research-bioreason.md)

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Exported on March 22, 2026 at 01:15 AM

Organism: Caenorhabditis elegans

Sequence:

MENLIPVVNKLQDVFATLGRKEDQIQLPQIVVVGSQSAGKSSVLENLVGRDFLPRGTGIVTRRPLILQLNHVALDDESKRRRSNGTLLTDDWAMFEHTGSKVFTDFDAVRKEIEDETDRVTGVNKGISLLPISLKIYSHRVVSLSLVDLPGITKIPVGDQPVNIEEQIREMILLYISNPSSIILAVTPANQDFATSEPIKLAREVDAGGQRTLAVLTKLDLMDQGTDAMDVLMGKVIPVKLGIIGVVNRSQQNILDNKLIVDAVKDEQSFMQKKYPTLASRNGTPYLAKRLNMLLMHHIRNCLPALKARVSIMNAQCQSDLVAFGEPVEDKNRTLLQIITRFATAYTSTIEGTARNIETTELCGGARICYIFHDTFGRSLESVNPLENLTQLDILTAIRNATGPRPALFVPEVSFELLVKRQIQRLEEPSLRCVELVHEEMQRMVQHCGFTTQQEMIRFPRLYDKINEVVSGVLKERLKPTNELVENLVAIELAYINTKHPEFTEANLVTLLKEELLLDDRHGRSRNRHASTGERAVSAHGEQQLQPVPGVNGVDLNAVLQQQQQQSQNQRASNGFLGLFGNAAASSKTSPQEKQSANFLPEVPETQLGRKLTSREQRDVAIIERLIRNYFIIVRKNIQDSVPKAIMALLVNFVRDNLQSELVRQLYKPDEMDDLLAETEDMAQRRRDTLETMKALQQASVIISEVRETQVW

Thinking Trace

I begin by dissecting the InterPro architecture and its order along the polypeptide. The N-terminus carries IPR001401 (Dynamin, GTPase domain, residues 1–304) and the overlapping IPR030381 (Dynamin-type guanine nucleotide-binding G domain, residues 24–304), together with IPR045063 (Dynamin, N-terminal domain, residues 30–219) and the conserved P-loop system flagged by IPR027417 (P-loop containing nucleoside triphosphate hydrolase homologous superfamily, residues 1–312) and the motif IPR019762 (Dynamin, GTPase region, conserved site, residues 53–62). This tightly clustered N-terminal module forms a classical P-loop NTPase engine that binds and hydrolyzes GTP. Mid-chain, IPR000375 (Dynamin stalk domain, residues 227–506) provides the oligomerization scaffold that assembles helical bundles and higher-order rings/spirals. The C-terminus contains IPR003130 (Dynamin GTPase effector domain, residues 615–706) and IPR020850 (GTPase effector domain, residues 620–711), which act as an intramolecular stimulator that accelerates assembly-dependent GTP hydrolysis. The overall family signature IPR022812 (Dynamin family, residues 2–706) confirms the full-length dynamin-like architecture: an N-terminal GTPase core, a central stalk for self-assembly, and a C-terminal effector module that couples assembly to catalysis.

This domain layout dictates molecular function. The paired GTPase/G-domain signatures (IPR001401, IPR030381) and P-loop superfamily (IPR027417) cause high-affinity GTP binding and regulated GTP hydrolysis; thus the primary molecular function is GTP binding and GTPase activity. The stalk domain (IPR000375) enforces cooperative assembly, and the effector modules (IPR003130, IPR020850) tune the kinetics so that polymerization stimulates catalysis. Together, this architecture specifies GO:0042802 molecular function as a dynamin-like P-loop NTPase whose activity is assembly-coupled.

From this chemistry flows the biological process. Dynamin-family assemblies typically drive constriction and scission of narrow membranes or organize membrane-associated remodeling. In Caenorhabditis elegans, the presence of the stalk and effector modules that enforce higher-order oligomers implies active remodeling at membrane necks and endocytic pits, consistent with membrane trafficking and cytoskeletal coupling. Therefore, the process aligns with membrane/cytoskeleton remodeling pathways that underlie endocytic uptake and vesicle formation, even if the precise pathway specialization can vary among metazoan dynamin homologs.

Cellular localization follows from the soluble, assembly-prone architecture. The absence of transmembrane segments and the reliance on oligomeric scaffolding place this protein in the cytoplasm, where it can transiently associate with membrane-rich substructures and cytoskeletal elements. This supports a cytoplasmic residency consistent with a peripheral, assembly-driven mechanism.

Mechanistically, the N-terminal GTPase core binds GTP and nucleates assembly via the stalk domain; assembly propagates catalytic acceleration through the C-terminal effector region, producing cycles of polymerization and GTP-driven conformational changes that remodel membranes. I hypothesize that it partners with endocytic adaptors and curvature-sensing factors to sculpt membrane necks and with cytoskeletal elements to coordinate vesicle budding and trafficking in the cytoplasm.

Functional Summary

A cytoplasmic dynamin-like P-loop NTPase that binds and hydrolyzes GTP to power self-assembly and membrane-remodeling cycles. Its N-terminal nucleotide-binding engine drives GTP-dependent conformational changes, the central stalk enforces oligomerization, and the C-terminal effector modules accelerate assembly-coupled catalysis. Together these features enable transient association with membrane-rich sites and cytoskeletal frameworks to support vesicle and trafficking pathways in the cytoplasm.

UniProt Summary

Exhibits GTPase activity.

InterPro Domains

Dynamin, GTPase domain (IPR001401, domain) — residues 1-304
P-loop containing nucleoside triphosphate hydrolase (IPR027417, homologous_superfamily) — residues 1-312
Dynamin (IPR022812, family) — residues 2-706
Dynamin-type guanine nucleotide-binding (G) domain (IPR030381, domain) — residues 24-304
Dynamin, N-terminal (IPR045063, domain) — residues 30-219
Dynamin, GTPase region, conserved site (IPR019762, conserved_site) — residues 53-62
Dynamin stalk domain (IPR000375, domain) — residues 227-506
Dynamin GTPase effector (IPR003130, domain) — residues 615-706
GTPase effector domain (IPR020850, domain) — residues 620-711

GO Terms

Molecular Function: molecular_function (GO:0003674), binding (GO:0005488), protein binding (GO:0005515), GO:0046983 (GO:0042802), protein dimerization activity (GO:0046983), protein homodimerization activity (GO:0042803)

Biological Process: biological_process (GO:0008150), developmental process (GO:0032502), cellular process (GO:0009987), multicellular organismal process (GO:0032501), GO:0032502 GO:0009987 (GO:0048856), cellular component organization or biogenesis (GO:0071840), multicellular organism development (GO:0007275), cell death (GO:0008219), embryo development (GO:0009790), cellular component organization (GO:0016043), programmed cell death (GO:0012501), organelle organization (GO:0006996), embryo development ending in birth or egg hatching (GO:0009792), apoptotic process (GO:0006915), mitochondrion organization (GO:0007005), apoptotic mitochondrial changes (GO:0008637), organelle fission (GO:0048285), mitochondrial fission (GO:0000266)

Cellular Component: cellular_component (GO:0005575), cellular anatomical entity (GO:0110165), intracellular anatomical structure (GO:0005622), organelle (GO:0043226), cytoplasm (GO:0005737), intracellular organelle (GO:0043229), mitochondrion (GO:0005739), membrane-bounded organelle (GO:0043227), intracellular membrane-bounded organelle (GO:0043231)

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Deep Research Bioreason Rl

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Exported on March 22, 2026 at 01:15 AM

Organism: Caenorhabditis elegans

Sequence:

MENLIPVVNKLQDVFATLGRKEDQIQLPQIVVVGSQSAGKSSVLENLVGRDFLPRGTGIVTRRPLILQLNHVALDDESKRRRSNGTLLTDDWAMFEHTGSKVFTDFDAVRKEIEDETDRVTGVNKGISLLPISLKIYSHRVVSLSLVDLPGITKIPVGDQPVNIEEQIREMILLYISNPSSIILAVTPANQDFATSEPIKLAREVDAGGQRTLAVLTKLDLMDQGTDAMDVLMGKVIPVKLGIIGVVNRSQQNILDNKLIVDAVKDEQSFMQKKYPTLASRNGTPYLAKRLNMLLMHHIRNCLPALKARVSIMNAQCQSDLVAFGEPVEDKNRTLLQIITRFATAYTSTIEGTARNIETTELCGGARICYIFHDTFGRSLESVNPLENLTQLDILTAIRNATGPRPALFVPEVSFELLVKRQIQRLEEPSLRCVELVHEEMQRMVQHCGFTTQQEMIRFPRLYDKINEVVSGVLKERLKPTNELVENLVAIELAYINTKHPEFTEANLVTLLKEELLLDDRHGRSRNRHASTGERAVSAHGEQQLQPVPGVNGVDLNAVLQQQQQQSQNQRASNGFLGLFGNAAASSKTSPQEKQSANFLPEVPETQLGRKLTSREQRDVAIIERLIRNYFIIVRKNIQDSVPKAIMALLVNFVRDNLQSELVRQLYKPDEMDDLLAETEDMAQRRRDTLETMKALQQASVIISEVRETQVW

Thinking Trace

Functional Summary

UniProt Summary

Exhibits GTPase activity.

InterPro Domains

Dynamin, GTPase domain (IPR001401, domain) — residues 1-304
P-loop containing nucleoside triphosphate hydrolase (IPR027417, homologous_superfamily) — residues 1-312
Dynamin (IPR022812, family) — residues 2-706
Dynamin-type guanine nucleotide-binding (G) domain (IPR030381, domain) — residues 24-304
Dynamin, N-terminal (IPR045063, domain) — residues 30-219
Dynamin, GTPase region, conserved site (IPR019762, conserved_site) — residues 53-62
Dynamin stalk domain (IPR000375, domain) — residues 227-506
Dynamin GTPase effector (IPR003130, domain) — residues 615-706
GTPase effector domain (IPR020850, domain) — residues 620-711

GO Terms

Generated by BioReason

Deep Research Falcon

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

provider: falcon
model: Edison Scientific Literature
cached: false
start_time: '2025-12-27T21:49:51.500266'
end_time: '2025-12-27T21:54:22.069987'
duration_seconds: 270.57
template_file: templates/gene_research_go_focused.md
template_variables:
organism: worm
gene_id: drp-1
gene_symbol: drp-1
uniprot_accession: Q8WQC9
protein_description: 'RecName: Full=Dynamin-1-like protein drp-1 {ECO:0000305};
EC=3.6.5.5 {ECO:0000250|UniProtKB:O00429}; AltName: Full=Dynamin-related protein
drp-1 {ECO:0000303|PubMed:10619028, ECO:0000312|WormBase:T12E12.4b};'
gene_info: Name=drp-1 {ECO:0000312|WormBase:T12E12.4b}; ORFNames=T12E12.4 {ECO:0000312|WormBase:T12E12.4b};
organism_full: Caenorhabditis elegans.
protein_family: Belongs to the TRAFAC class dynamin-like GTPase
protein_domains: Dynamin. (IPR022812); Dynamin_GTPase. (IPR001401); Dynamin_GTPase_CS.
(IPR019762); Dynamin_N. (IPR045063); Dynamin_stalk. (IPR000375)
provider_config:
timeout: 600
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parameters:
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temperature: 0.1
citation_count: 19

Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: Q8WQC9
Protein Description: RecName: Full=Dynamin-1-like protein drp-1 {ECO:0000305}; EC=3.6.5.5 {ECO:0000250|UniProtKB:O00429}; AltName: Full=Dynamin-related protein drp-1 {ECO:0000303|PubMed:10619028, ECO:0000312|WormBase:T12E12.4b};
Gene Information: Name=drp-1 {ECO:0000312|WormBase:T12E12.4b}; ORFNames=T12E12.4 {ECO:0000312|WormBase:T12E12.4b};
Organism (full): Caenorhabditis elegans.
Protein Family: Belongs to the TRAFAC class dynamin-like GTPase
Key Domains: Dynamin. (IPR022812); Dynamin_GTPase. (IPR001401); Dynamin_GTPase_CS. (IPR019762); Dynamin_N. (IPR045063); Dynamin_stalk. (IPR000375)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "drp-1" matches the protein description above
Verify the organism is correct: Caenorhabditis elegans.
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'drp-1' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

Research Target:

Please provide a comprehensive research report on the gene drp-1 (gene ID: drp-1, UniProt: Q8WQC9) in worm.

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.

Output

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: Q8WQC9
Protein Description: RecName: Full=Dynamin-1-like protein drp-1 {ECO:0000305}; EC=3.6.5.5 {ECO:0000250|UniProtKB:O00429}; AltName: Full=Dynamin-related protein drp-1 {ECO:0000303|PubMed:10619028, ECO:0000312|WormBase:T12E12.4b};
Gene Information: Name=drp-1 {ECO:0000312|WormBase:T12E12.4b}; ORFNames=T12E12.4 {ECO:0000312|WormBase:T12E12.4b};
Organism (full): Caenorhabditis elegans.
Protein Family: Belongs to the TRAFAC class dynamin-like GTPase
Key Domains: Dynamin. (IPR022812); Dynamin_GTPase. (IPR001401); Dynamin_GTPase_CS. (IPR019762); Dynamin_N. (IPR045063); Dynamin_stalk. (IPR000375)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "drp-1" matches the protein description above
Verify the organism is correct: Caenorhabditis elegans.
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Please provide a comprehensive research report on the gene drp-1 (gene ID: drp-1, UniProt: Q8WQC9) in worm.

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.

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.

Plan summary and verification
- Identity verification: We confirm that the target is C. elegans drp-1 (UniProt Q8WQC9), a TRAFAC class dynamin-like GTPase. In C. elegans, drp-1 encodes the sole, canonical mitochondrial fission GTPase; loss-of-function alleles such as drp-1(tm1108), deleting part of the GTPase domain, are widely used for functional studies (e.g., mitochondrial morphology, organismal phenotypes) (byrne2019disruptionofmitochondrial pages 1-2). Mechanistic properties of Drp1/dynamin-related proteins, including GTPase-driven assembly and membrane scission, are conserved and established in cross-species studies (kamerkar2018dynaminrelatedprotein1 pages 1-2). The organism is confirmed as Caenorhabditis elegans in all C. elegans primary sources cited below (byrne2019disruptionofmitochondrial pages 1-2, scholtes2018drp1mediatedapoptosisinduces pages 3-5, scholtes2018drp1mediatedapoptosisinduces pages 5-6, scholtes2018drp1mediatedapoptosisinduces pages 10-11). No conflicting gene symbol usage was found in other organisms in the evidence set; thus, we proceed with C. elegans drp-1.

Key concepts and definitions
- Protein class and domains: DRP-1 is a dynamin-related, large GTPase. Like other Drp1 orthologs, it oligomerizes into spirals at mitochondrial constriction sites and hydrolyzes GTP to power membrane constriction and scission. Drp1 lacks the classical dynamin PH domain but contains a variable B-insert implicated in adaptor/lipid interactions; these features underlie membrane binding, self-assembly, and catalysis (cross-species) (https://doi.org/10.1038/s41467-018-07543-w, Dec 2018) (kamerkar2018dynaminrelatedprotein1 pages 1-2). In C. elegans, the tm1108 allele removes 407 bp within the GTPase domain, yielding a strong loss-of-function (https://doi.org/10.1007/s00018-019-03024-5, Mar 2019) (byrne2019disruptionofmitochondrial pages 1-2).
- Primary function: DRP-1 catalyzes mitochondrial (and peroxisomal, by inference) fission by binding the outer mitochondrial membrane (OMM), oligomerizing, and coupling GTP hydrolysis to membrane constriction and scission (https://doi.org/10.1038/s41467-018-07543-w, Dec 2018) (kamerkar2018dynaminrelatedprotein1 pages 1-2). In C. elegans, DRP-1 governs mitochondrial network morphology; reducing DRP-1 activity causes enlarged, interconnected mitochondria, while overexpression increases fragmentation (https://doi.org/10.1007/s00018-019-03024-5, Mar 2019; https://doi.org/10.1038/s41598-018-25727-8, May 2018) (byrne2019disruptionofmitochondrial pages 1-2, scholtes2018drp1mediatedapoptosisinduces pages 3-5).

Biochemical reaction and substrate specificity
- Reaction: DRP-1 is a P-loop NTPase that hydrolyzes GTP to GDP + Pi; assembly-stimulated GTPase activity drives conformational changes that constrict and sever membranes. In reconstitution, Drp1 alone can sever tubes up to ~250 nm radius, with scission requiring membrane binding, self-assembly, and GTP hydrolysis (https://doi.org/10.1038/s41467-018-07543-w, Dec 2018) (kamerkar2018dynaminrelatedprotein1 pages 1-2). Substrate specificity is membrane contextual: DRP-1 binds mitochondrial/peroxisomal membranes via adaptors and lipid interactions; it does not require dynamin-2 for fission in reconstitution and cell systems (kamerkar2018dynaminrelatedprotein1 pages 1-2).

Cellular and subcellular localization and recruitment
- Localization: DRP-1 resides largely in the cytosol and is recruited to the OMM at fission sites. In metazoans, recruitment involves OMM adaptors such as Mff and MiD proteins; worm literature supports roles for worm FIS-1/FIS-2 and MFF-1/MFF-2 in recruiting/organizing DRP-1 at constriction sites (https://doi.org/10.1007/s11357-024-01276-z, Jul 2025; https://doi.org/10.1007/s00018-019-03024-5, Mar 2019) (traa2025developmentaldisruptionof pages 1-3, byrne2019disruptionofmitochondrial pages 1-2). Cross-species mechanistic studies confirm Drp1’s assembly at membrane contact sites and scission sufficiency (kamerkar2018dynaminrelatedprotein1 pages 1-2).

Pathways and roles in apoptosis, mitophagy, stress, development, and lifespan
- Apoptosis: C. elegans DRP-1 promotes apoptosis-linked mitochondrial fragmentation and can act downstream of the caspase CED-3. In a dystrophin-deficient model, DRP-1 is cleaved by CED-3, and this cleavage is required for dystrophin- and age-dependent muscle degeneration; loss of drp-1 reduces TUNEL-positive muscle cells from 5.28 ± 0.26 to ~2.07 ± 0.19 per animal (https://doi.org/10.1038/s41598-018-25727-8, May 2018) (scholtes2018drp1mediatedapoptosisinduces pages 5-6, scholtes2018drp1mediatedapoptosisinduces pages 10-11). Earlier embryonic work showed drp-1 overexpression triggers mitochondrial fragmentation independent of caspase activation but requires egl-1, ced-4, and ced-3 to induce cell death; ced-9 gain-of-function blocks DRP-1-induced fragmentation, positioning CED-9 upstream in controlling mitochondrial morphology during cell death signaling (https://doi.org/10.5282/edoc.4281, 2005) (jagasia2005mitochondrialdynamicsin pages 110-116).
- Mitophagy and stress responses: Toxicant stress (CoCl2) upregulates drp-1 and induces DRP-1–dependent mitochondrial fragmentation; genetic or pharmacologic DRP-1 inhibition reduces ROS, ameliorates growth defects, and improves survival, linking DRP-1 activity to oxidative stress and toxicity outcomes (https://doi.org/10.1093/toxsci/kfaa105, Jun 2020) (zheng2020drp1dependentmitochondrial pages 14-14). In insulin/IGF-1 signaling (IIS) mutant daf-2, developmental drp-1 disruption increases mitophagy and stress resistance and contributes to lifespan extension (https://doi.org/10.1007/s11357-024-01276-z, Jul 2025) (traa2025developmentaldisruptionof pages 1-3).
- Development, behavior and lifespan: Systematic analysis shows loss of fission or fusion regulators yields progressive, age-dependent defects in movement and neuromuscular function; fusion loss causes more severe defects, whereas fission becomes particularly important later in life to mitigate aging-related stress. Disruption of either process reduces median lifespan without altering maximal lifespan (https://doi.org/10.1007/s00018-019-03024-5, Mar 2019) (byrne2019disruptionofmitochondrial pages 1-2). In an IIS-long-lived background, drp-1 disruption during development further extends longevity and enhances OXPHOS and ATP levels while increasing mitochondrial/peroxisomal connectedness; mitophagy contributes to the lifespan benefit (https://doi.org/10.1007/s11357-024-01276-z, Jul 2025) (traa2025developmentaldisruptionof pages 1-3).

Interacting partners and upstream regulation in C. elegans
- Apoptotic network: DRP-1 intersects the canonical apoptosis pathway. Evidence points to DRP-1 cleavage by CED-3, with roles for CED-9 (BCL2-like), and downstream nucleases/apoptosis factors such as CPS-6 (EndoG), WAH-1 (AIF), NUC-1, CRN-2/6 and engulfment genes (ced-1, psr-1) shaping cell death and muscle degeneration phenotypes (https://doi.org/10.1038/s41598-018-25727-8, May 2018; https://doi.org/10.5282/edoc.4281, 2005) (scholtes2018drp1mediatedapoptosisinduces pages 10-11, jagasia2005mitochondrialdynamicsin pages 110-116). Quantitatively, RNAi against apoptosis/engulfment factors reduces abnormal cell counts and modifies mitochondrial morphology metrics in dystrophin mutants (scholtes2018drp1mediatedapoptosisinduces pages 10-11).
- Mitochondrial fission apparatus: Worm DRP-1 operates with OMM adaptors. Cross-species work identifies Mff and MiD proteins as direct recruiters; worm studies implicate FIS-1/FIS-2 and MFF-1/MFF-2 as functional analogs contributing to DRP-1 recruitment (https://doi.org/10.1038/s41467-018-07543-w, Dec 2018; https://doi.org/10.1007/s11357-024-01276-z, Jul 2025) (kamerkar2018dynaminrelatedprotein1 pages 1-2, traa2025developmentaldisruptionof pages 1-3).

Recent developments and latest research
- While the most detailed mechanistic biochemistry remains from 2018–2020 cross-species work, organismal C. elegans studies through 2019–2020 and a 2025 study continue to resolve the interplay between DRP-1-mediated fission, stress responses, mitophagy, and lifespan in defined genetic backgrounds (IIS), including quantitative links to OXPHOS and ATP levels, and the requirement for developmental timing (https://doi.org/10.1007/s00018-019-03024-5, Mar 2019; https://doi.org/10.1093/toxsci/kfaa105, Jun 2020; https://doi.org/10.1007/s11357-024-01276-z, Jul 2025) (byrne2019disruptionofmitochondrial pages 1-2, zheng2020drp1dependentmitochondrial pages 14-14, traa2025developmentaldisruptionof pages 1-3). We did not identify C. elegans-specific drp-1 primary literature explicitly dated 2023–2024 in the available evidence; this likely reflects limited worm-specific publications in those years, though adjacent fields reported methodological and review advances.

Relevant statistics and quantitative data
- Mitochondrial morphology in dystrophin mutants: Circularity index increases from ~0.52 ± 0.009 (WT) to ~0.75 ± 0.014; drp-1 loss reduces circularity in the dystrophic background to ~0.65 ± 0.014, indicating partial rescue of fragmentation (https://doi.org/10.1038/s41598-018-25727-8, May 2018) (scholtes2018drp1mediatedapoptosisinduces pages 5-6).
- Apoptosis readouts: TUNEL-positive muscle cells decrease from 5.28 ± 0.26 (dys-1;hlh-1) to ~2.07 ± 0.19 with drp-1 deletion; drp-1 overexpression in embryos increases cell corpses to an average of 55.4 (vs ~7.3 WT), showing potent pro-death consequences when DRP-1 is hyperactive (https://doi.org/10.1038/s41598-018-25727-8, May 2018; https://doi.org/10.5282/edoc.4281, 2005) (scholtes2018drp1mediatedapoptosisinduces pages 5-6, jagasia2005mitochondrialdynamicsin pages 110-116).
- Lifespan and healthspan: Loss of fission or fusion regulators reduces median lifespan without changing maximal lifespan; drp-1 disruption specifically during development extends longevity in daf-2 IIS mutants and increases stress resistance and mitophagy; precise magnitude depends on protocol but the effect is described as drastic in extending the already long daf-2 lifespan (https://doi.org/10.1007/s00018-019-03024-5, Mar 2019; https://doi.org/10.1007/s11357-024-01276-z, Jul 2025) (byrne2019disruptionofmitochondrial pages 1-2, traa2025developmentaldisruptionof pages 1-3).
- Stress toxicity: Under CoCl2 exposure, drp-1 upregulation and DRP-1–dependent fragmentation mediate increased ROS and decreased survival; inhibition of drp-1 suppresses ROS and rescues growth and survival defects (https://doi.org/10.1093/toxsci/kfaa105, Jun 2020) (zheng2020drp1dependentmitochondrial pages 14-14).

Current applications and real-world implementations
- Experimental tools: C. elegans drp-1(tm1108) null and dominant-negative mutants, mitochondrial matrix GFP reporters (e.g., ccIs4251), dystrophin-deficient models (dys-1;hlh-1), and toxicology paradigms (CoCl2) enable quantitative dissection of DRP-1 function in vivo (https://doi.org/10.1038/s41598-018-25727-8, May 2018; https://doi.org/10.1007/s00018-019-03024-5, Mar 2019; https://doi.org/10.1093/toxsci/kfaa105, Jun 2020) (scholtes2018drp1mediatedapoptosisinduces pages 3-5, byrne2019disruptionofmitochondrial pages 1-2, zheng2020drp1dependentmitochondrial pages 14-14).
- Cross-species biochemical inference: Reconstitution of Drp1 membrane fission provides mechanistic constraints—Drp1 alone can constrict and sever membranes in a GTP-dependent manner, and Dnm2 is dispensable—informing interpretation of worm phenotypes and adaptor dependence (https://doi.org/10.1038/s41467-018-07543-w, Dec 2018) (kamerkar2018dynaminrelatedprotein1 pages 1-2).

Expert opinions and analysis
- The integrated view from organismal and biochemical studies is that DRP-1’s principal role is to execute mitochondrial fission, with context-dependent roles in apoptosis and stress adaptation. In C. elegans, DRP-1’s apoptotic function appears to be regulated by caspase CED-3 cleavage and constrained by CED-9, while its homeostatic role coordinates with mitophagy to rebuild or cull mitochondria under stress. The developmental timing of drp-1 disruption is critical for lifespan effects in IIS mutants, highlighting a systems-level coupling between mitochondrial dynamics, cellular quality control, and organismal aging (scholtes2018drp1mediatedapoptosisinduces pages 10-11, byrne2019disruptionofmitochondrial pages 1-2, traa2025developmentaldisruptionof pages 1-3, zheng2020drp1dependentmitochondrial pages 14-14).

Embedded summary table
| Aspect | Key Findings | Experimental context/model | Year & Source (journal, DOI URL) |
|---|---|---|---|
| Identity / domains | Dynamin-family GTPase with conserved GTPase domain; tm1108 is a 407 bp deletion within the GTPase domain used as a loss-of-function allele (affects GTPase activity). (kamerkar2018dynaminrelatedprotein1 pages 1-2, byrne2019disruptionofmitochondrial pages 1-2) | Molecular annotation and genetic studies in C. elegans; allele characterization (tm1108). | Kamerkar et al., Nat Commun 2018; https://doi.org/10.1038/s41467-018-07543-w; Byrne et al., Cell Mol Life Sci 2019; https://doi.org/10.1007/s00018-019-03024-5 |
| Primary function | GTP hydrolysis–driven membrane constriction and scission that mediates mitochondrial and peroxisomal fission; Drp1 can be sufficient to constrict/sever membranes in vitro. (kamerkar2018dynaminrelatedprotein1 pages 1-2, byrne2019disruptionofmitochondrial pages 1-2) | Reconstitution and cell biological assays; C. elegans loss-of-function and in vitro membrane-tube assays. | Kamerkar et al., Nat Commun 2018; https://doi.org/10.1038/s41467-018-07543-w; Byrne et al., Cell Mol Life Sci 2019; https://doi.org/10.1007/s00018-019-03024-5 |
| Localization / recruitment | Recruited from cytosol to outer mitochondrial membrane by adaptor proteins (Mff/MiD families in other species); in worm, reported adaptors include FIS-1, FIS-2 and MFF-1/MFF-2. (kamerkar2018dynaminrelatedprotein1 pages 1-2, traa2025developmentaldisruptionof pages 1-3, byrne2019disruptionofmitochondrial pages 1-2) | Localization and genetic interaction studies in C. elegans and cross-species biochemical reconstitution. | Kamerkar et al., Nat Commun 2018; https://doi.org/10.1038/s41467-018-07543-w; Traa et al., GeroScience 2025; https://doi.org/10.1007/s11357-024-01276-z |
| Apoptosis role | Acts downstream of caspase CED-3 and is cleaved by CED-3; cleavage is required for dystrophin-dependent muscle degeneration. Loss of drp-1 reduces TUNEL-positive muscle cells (from 5.28 ± 0.26 to ~2.07 ± 0.19). (scholtes2018drp1mediatedapoptosisinduces pages 10-11, scholtes2018drp1mediatedapoptosisinduces pages 5-6, jagasia2005mitochondrialdynamicsin pages 110-116) | Genetic loss- and gain-of-function (drp-1 null, dominant K40A, overexpression) and TUNEL assays in dystrophin mutant worms. | Scholtes et al., Sci Rep 2018; https://doi.org/10.1038/s41598-018-25727-8; Jagasia dissertation 2005; https://doi.org/10.5282/edoc.4281 |
| Mitophagy & stress | DRP-1 coordinates fission with autophagy/mitophagy during stress; CoCl2 upregulates drp-1 and DRP-1–dependent fragmentation contributes to toxicity (inhibition of drp-1 reduces ROS and rescues survival); in daf-2;drp-1 increased mitophagy observed. (zheng2020drp1dependentmitochondrial pages 14-14, traa2025developmentaldisruptionof pages 1-3) | Toxicant exposure (CoCl2), genetic perturbation, mitophagy and ROS assays; lifespan/rescue experiments. | Zheng et al., Toxicol Sci 2020; https://doi.org/10.1093/toxsci/kfaa105; Traa et al., GeroScience 2025; https://doi.org/10.1007/s11357-024-01276-z |
| Development & lifespan | drp-1 disruption during development extends daf-2 (IIS) mutant longevity; in wild-type, loss of fission regulators reduces median lifespan but not maximal lifespan. (traa2025developmentaldisruptionof pages 1-3, byrne2019disruptionofmitochondrial pages 1-2) | Developmental/tissue-specific RNAi and genetic knockouts; lifespan assays in wild-type and daf-2 backgrounds. | Traa et al., GeroScience 2025; https://doi.org/10.1007/s11357-024-01276-z; Byrne et al., Cell Mol Life Sci 2019; https://doi.org/10.1007/s00018-019-03024-5 |
| Quantitative morphology metrics | Example metrics: mitochondrial circularity — wild-type ~0.52 ± 0.009 vs dystrophic ~0.75 ± 0.014; drp-1 loss in dystrophic background reduces circularity to ~0.65 ± 0.014. Overexpression of drp-1 in embryos increases cell corpses (avg ~55.4 vs WT ~7.3). (scholtes2018drp1mediatedapoptosisinduces pages 5-6, scholtes2018drp1mediatedapoptosisinduces pages 10-11, jagasia2005mitochondrialdynamicsin pages 110-116) | Confocal imaging with mitochondrial matrix GFP reporters (e.g., ccIs4251), morphometry and embryonic cell-corpse counts. | Scholtes et al., Sci Rep 2018; https://doi.org/10.1038/s41598-018-25727-8; Jagasia dissertation 2005; https://doi.org/10.5282/edoc.4281 |
| Interactors / adaptors | Genetic and biochemical network includes CED-3, CED-9 (regulates fragmentation), CPS-6, WAH-1, engulfment genes (ced-1, psr-1) and worm fission factors FIS-1/FIS-2/MFF-1; cross-species adaptors (Mff, MiD49/51) recruit Drp1 biochemically. (scholtes2018drp1mediatedapoptosisinduces pages 10-11, traa2025developmentaldisruptionof pages 1-3, kamerkar2018dynaminrelatedprotein1 pages 1-2) | Genetic interaction screens, RNAi perturbations and cross-species biochemical studies. | Scholtes et al., Sci Rep 2018; https://doi.org/10.1038/s41598-018-25727-8; Traa et al., GeroScience 2025; https://doi.org/10.1007/s11357-024-01276-z; Kamerkar et al., Nat Commun 2018; https://doi.org/10.1038/s41467-018-07543-w |
| Applications / real-world implementations | Widely used genetic tools (tm1108 null, dominant mutants), mitochondrial reporters (ccIs4251), quantitative imaging pipelines and C. elegans disease/toxicity models (dystrophin mutants, CoCl2 exposure) to study mitochondrial dynamics and organismal phenotypes. (scholtes2018drp1mediatedapoptosisinduces pages 3-5, byrne2019disruptionofmitochondrial pages 1-2, zheng2020drp1dependentmitochondrial pages 14-14) | Model organism genetic studies, live imaging, toxicology and aging research. | Scholtes et al., Sci Rep 2018; https://doi.org/10.1038/s41598-018-25727-8; Byrne et al., Cell Mol Life Sci 2019; https://doi.org/10.1007/s00018-019-03024-5; Zheng et al., Toxicol Sci 2020; https://doi.org/10.1093/toxsci/kfaa105 |

Table: Concise, citable summary of key properties, functions, quantitative metrics and experimental contexts for C. elegans drp-1 (UniProt Q8WQC9), with source DOIs for each entry; useful as a quick-reference for functional annotation and experimental planning.

Conclusion
C. elegans drp-1 (Q8WQC9) encodes the conserved dynamin-like GTPase governing mitochondrial fission. DRP-1 is recruited from the cytosol to the OMM by adaptors, oligomerizes at constriction sites, and uses assembly-stimulated GTP hydrolysis to constrict and sever mitochondrial (and peroxisomal) membranes. In worms, DRP-1 shapes mitochondrial networks across tissues, contributes to apoptosis downstream of CED-3, coordinates with autophagy/mitophagy during stress, and, depending on developmental context and genetic background (IIS), modulates lifespan. Quantitative evidence links DRP-1 to mitochondrial fragmentation metrics, apoptosis indices, stress resistance, and lifespan distributions. Together, cross-species biochemical mechanisms and worm in vivo genetics provide a coherent functional annotation for drp-1 in localization, mechanism, and pathway integration (kamerkar2018dynaminrelatedprotein1 pages 1-2, byrne2019disruptionofmitochondrial pages 1-2, scholtes2018drp1mediatedapoptosisinduces pages 10-11, scholtes2018drp1mediatedapoptosisinduces pages 5-6, zheng2020drp1dependentmitochondrial pages 14-14, traa2025developmentaldisruptionof pages 1-3, scholtes2018drp1mediatedapoptosisinduces pages 3-5, jagasia2005mitochondrialdynamicsin pages 110-116).

References

(byrne2019disruptionofmitochondrial pages 1-2): Joseph J. Byrne, Ming S. Soh, Gursimran Chandhok, Tarika Vijayaraghavan, Jean-Sébastien Teoh, Simon Crawford, Ansa E. Cobham, Nethmi M. B. Yapa, Christen K. Mirth, and Brent Neumann. Disruption of mitochondrial dynamics affects behaviour and lifespan in caenorhabditis elegans. Cellular and Molecular Life Sciences: CMLS, 76:1967-1985, Mar 2019. URL: https://doi.org/10.1007/s00018-019-03024-5, doi:10.1007/s00018-019-03024-5. This article has 114 citations.
(kamerkar2018dynaminrelatedprotein1 pages 1-2): Sukrut C. Kamerkar, Felix Kraus, Alice J. Sharpe, Thomas J. Pucadyil, and Michael T. Ryan. Dynamin-related protein 1 has membrane constricting and severing abilities sufficient for mitochondrial and peroxisomal fission. Nature Communications, Dec 2018. URL: https://doi.org/10.1038/s41467-018-07543-w, doi:10.1038/s41467-018-07543-w. This article has 273 citations and is from a highest quality peer-reviewed journal.
(scholtes2018drp1mediatedapoptosisinduces pages 3-5): Charlotte Scholtes, Stéphanie Bellemin, Edwige Martin, Maïté Carre-Pierrat, Bertrand Mollereau, Kathrin Gieseler, and Ludivine Walter. Drp-1-mediated apoptosis induces muscle degeneration in dystrophin mutants. Scientific Reports, May 2018. URL: https://doi.org/10.1038/s41598-018-25727-8, doi:10.1038/s41598-018-25727-8. This article has 26 citations and is from a peer-reviewed journal.
(scholtes2018drp1mediatedapoptosisinduces pages 5-6): Charlotte Scholtes, Stéphanie Bellemin, Edwige Martin, Maïté Carre-Pierrat, Bertrand Mollereau, Kathrin Gieseler, and Ludivine Walter. Drp-1-mediated apoptosis induces muscle degeneration in dystrophin mutants. Scientific Reports, May 2018. URL: https://doi.org/10.1038/s41598-018-25727-8, doi:10.1038/s41598-018-25727-8. This article has 26 citations and is from a peer-reviewed journal.
(scholtes2018drp1mediatedapoptosisinduces pages 10-11): Charlotte Scholtes, Stéphanie Bellemin, Edwige Martin, Maïté Carre-Pierrat, Bertrand Mollereau, Kathrin Gieseler, and Ludivine Walter. Drp-1-mediated apoptosis induces muscle degeneration in dystrophin mutants. Scientific Reports, May 2018. URL: https://doi.org/10.1038/s41598-018-25727-8, doi:10.1038/s41598-018-25727-8. This article has 26 citations and is from a peer-reviewed journal.
(traa2025developmentaldisruptionof pages 1-3): Annika Traa, Aura A. Tamez González, and Jeremy M. Van Raamsdonk. Developmental disruption of the mitochondrial fission gene drp-1 extends the longevity of daf-2 insulin/igf-1 receptor mutant. GeroScience, 47:877-902, Jul 2025. URL: https://doi.org/10.1007/s11357-024-01276-z, doi:10.1007/s11357-024-01276-z. This article has 6 citations and is from a peer-reviewed journal.
(jagasia2005mitochondrialdynamicsin pages 110-116): Ravi Jagasia. Mitochondrial dynamics in caenorhabditis elegans programmed cell death. Dissertation, Jan 2005. URL: https://doi.org/10.5282/edoc.4281, doi:10.5282/edoc.4281. This article has 0 citations.
(zheng2020drp1dependentmitochondrial pages 14-14): Fuli Zheng, Pan Chen, Huangyuan Li, and Michael Aschner. Drp-1 dependent mitochondrial fragmentation contributes to cobalt chloride induced toxicity in caenorhabditis elegans. Toxicological sciences : an official journal of the Society of Toxicology, 177:158-167, Jun 2020. URL: https://doi.org/10.1093/toxsci/kfaa105, doi:10.1093/toxsci/kfaa105. This article has 23 citations.

Citations

byrne2019disruptionofmitochondrial pages 1-2
jagasia2005mitochondrialdynamicsin pages 110-116
traa2025developmentaldisruptionof pages 1-3
https://doi.org/10.1038/s41467-018-07543-w,
https://doi.org/10.1007/s00018-019-03024-5,
https://doi.org/10.1038/s41598-018-25727-8,
https://doi.org/10.1007/s11357-024-01276-z,
https://doi.org/10.5282/edoc.4281,
https://doi.org/10.1093/toxsci/kfaa105,
https://doi.org/10.1038/s41467-018-07543-w;
https://doi.org/10.1007/s00018-019-03024-5
https://doi.org/10.1007/s11357-024-01276-z
https://doi.org/10.1038/s41598-018-25727-8;
https://doi.org/10.5282/edoc.4281
https://doi.org/10.1093/toxsci/kfaa105;
https://doi.org/10.1007/s11357-024-01276-z;
https://doi.org/10.1038/s41467-018-07543-w
https://doi.org/10.1007/s00018-019-03024-5;
https://doi.org/10.1093/toxsci/kfaa105

Bioreason Rl Review

(drp-1-bioreason-rl-review.md)

BioReason-Pro RL Review: drp-1 (C. elegans)

Source: drp-1-deep-research-bioreason-rl.md

Correctness: 3/5
Completeness: 2/5

Functional Summary Review

The BioReason functional summary states:

A cytoplasmic dynamin-like P-loop NTPase that binds and hydrolyzes GTP to power self-assembly and membrane-remodeling cycles. Its N-terminal nucleotide-binding engine drives GTP-dependent conformational changes, the central stalk enforces oligomerization, and the C-terminal effector modules accelerate assembly-coupled catalysis. Together these features enable transient association with membrane-rich sites and cytoskeletal frameworks to support vesicle and trafficking pathways in the cytoplasm.

The molecular function description is largely correct: DRP-1 is indeed a dynamin-related GTPase with GTP binding and hydrolysis activity (GO:0003924, GO:0005525), and the domain architecture -- GTPase core, stalk for oligomerization, GTPase effector domain -- is accurately described. The cytoplasmic localization is also correct (GO:0005737).

However, there is a significant error in the biological process assignment. BioReason describes DRP-1 as supporting "vesicle and trafficking pathways," which conflates DRP-1 with classical dynamins involved in endocytosis. The curated review is very clear: DRP-1 is specifically a mitochondrial fission factor (GO:0000266). Its core function is controlling scission of the mitochondrial outer membrane (PMID:10619028). The curated review explicitly marks the IBA annotations for microtubule binding and microtubule localization as MARK_AS_OVER_ANNOTATED because they derive from the broader dynamin family rather than the DRP-1/Drp1 subfamily.

Additional biology missed:
- DRP-1 is recruited from cytosol to mitochondrial outer membrane at constriction sites
- Role in apoptosis downstream of caspase CED-3 (mitochondrial elimination in dying cells)
- Peroxisome fission (by inference from mammalian orthologs)
- DRP-1 cleavage by CED-3 separates fission and apoptotic functions

Comparison with interpro2go:

The interpro2go annotation (GO_REF:0000002) assigns GO:0003924 (GTPase activity), which BioReason correctly captures. However, BioReason makes the same error that the curated review flags in IBA annotations -- attributing endocytic/vesicle trafficking functions from the broader dynamin family to DRP-1, rather than the mitochondria-specific fission function that defines this subfamily.

Notes on thinking trace

The trace accurately dissects the dynamin domain architecture but then generalizes to "membrane trafficking and cytoskeletal coupling" and "endocytic uptake and vesicle formation." The reasoning acknowledges that "the precise pathway specialization can vary among metazoan dynamin homologs" but fails to resolve this to the mitochondrial fission specialization that is the actual biology of DRP-1.

📄 View Raw YAML

id: Q8WQC9
gene_symbol: drp-1
aliases:
- T12E12.4
- Dynamin-related protein 1
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:6239
  label: Caenorhabditis elegans
description: DRP-1 is a dynamin-related GTPase that mediates mitochondrial outer membrane
  fission in C. elegans. It is recruited from the cytosol to the mitochondrial outer
  membrane at sites of constriction, where it oligomerizes and uses GTP hydrolysis
  to drive membrane scission. DRP-1 is essential for normal mitochondrial division
  and morphology; loss of function causes enlarged, interconnected mitochondria with
  matrix retracted into blebs connected by outer membrane tubules (PMID:10619028).
  DRP-1 also plays roles in apoptosis downstream of caspase CED-3, where it promotes
  mitochondrial fragmentation and elimination in dying cells (PMID:18722182, PMID:15716954).
  DRP-1 is cleaved by CED-3, and this cleavage is required for its pro-apoptotic but
  not its fission function (PMID:18722182). The protein coordinates with autophagy/mitophagy
  during stress responses and influences lifespan in the context of insulin/IGF-1
  signaling. By similarity to mammalian DRP1, it likely also mediates peroxisome fission.
existing_annotations:
- term:
    id: GO:0003924
    label: GTPase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: DRP-1 is a dynamin-related GTPase with conserved GTPase domains. The
      protein contains a Dynamin-type G domain (aa 24-304) with G1-G5 motifs characteristic
      of GTPases. Mutations in conserved GTPase domain residues (K40A, V43F, T61A)
      cause disrupted mitochondrial morphology (PMID:10619028), indicating GTPase
      activity is essential for function. Cross-species biochemical studies confirm
      Drp1 GTPase activity is assembly-stimulated and required for membrane scission.
    action: ACCEPT
    reason: Core molecular function supported by domain architecture and mutational
      analysis. The K40A mutation in the GTPase domain causes 80% of cells to have
      irregular mitochondria (PMID:10619028). IBA annotation is appropriate given
      strong phylogenetic conservation of this function in the dynamin superfamily.
    supported_by:
    - reference_id: PMID:10619028
      supporting_text: Mutant DRP-1 causes the mitochondrial matrix to retract into
        large blebs that are both surrounded and connected by tubules of outer membrane.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: DRP-1 localizes to the cytosol and is recruited to mitochondria at fission
      sites. UniProt annotation confirms cytosol localization with experimental evidence
      (PMID:21949250).
    action: ACCEPT
    reason: Consistent with cytosolic localization before recruitment to mitochondrial
      membrane. DRP-1 exists in cytosolic pools and is recruited to mitochondria upon
      fission signals, which is a general feature of dynamin-related proteins.
    supported_by:
    - reference_id: PMID:21949250
      supporting_text: the EGL-1-CED-9 complex promotes mitochondrial fission by recruiting
        DRP-1 to mitochondria
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: DRP-1 associates with membranes, specifically the mitochondrial outer
      membrane where it mediates fission. The term 'membrane' is very general.
    action: ACCEPT
    reason: DRP-1 does associate with membranes (mitochondrial outer membrane specifically).
      While more specific terms exist, this IBA annotation captures a broad but accurate
      property of the protein. The more specific annotation to mitochondrial outer
      membrane is also present.
    supported_by:
    - reference_id: PMID:10619028
      supporting_text: DRP-1 fused to GFP is observed in spots on mitochondria where
        scission eventually occurs.
- term:
    id: GO:0000266
    label: mitochondrial fission
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Mitochondrial fission is the core biological process function of DRP-1.
      Multiple experimental studies demonstrate DRP-1 is required for mitochondrial
      outer membrane scission (PMID:10619028, PMID:19327994, PMID:18827010).
    action: ACCEPT
    reason: This is the primary, defining function of DRP-1. Loss of DRP-1 function
      causes inhibition of mitochondrial outer membrane scission, while overexpression
      causes excessive fragmentation (PMID:10619028). This function is well-conserved
      across eukaryotes in the dynamin-related protein family.
    supported_by:
    - reference_id: PMID:10619028
      supporting_text: wild-type DRP-1 contributes to the final stages of mitochondrial
        division by controlling scission of the mitochondrial outer membrane.
- term:
    id: GO:0048312
    label: intracellular distribution of mitochondria
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: DRP-1 mutants show abnormal mitochondrial distribution. The fission function
      of DRP-1 contributes to proper mitochondrial inheritance and distribution. UniProt
      notes disruption phenotype includes disorganized gonads with abnormal mitochondrial
      distribution (PMID:10619028).
    action: ACCEPT
    reason: The annotation is appropriate as mitochondrial fission is necessary for
      proper distribution of mitochondria during cell division and within cells. Loss
      of drp-1 causes disorganized gonads with abnormal mitochondrial distribution.
    supported_by:
    - reference_id: PMID:10619028
      supporting_text: mitochondria are disrupted by mutations in a C. elegans dynamin-related
        protein (DRP-1).
- term:
    id: GO:0016559
    label: peroxisome fission
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Peroxisome fission function is inferred by similarity to mammalian DRP1/DNM1L
      which is well-documented to mediate peroxisome fission. UniProt annotates this
      function with ISS evidence (ECO:0000250|UniProtKB:O00429).
    action: ACCEPT
    reason: Mammalian DRP1 is established to mediate both mitochondrial and peroxisomal
      fission using the same membrane scission mechanism. The IBA annotation is phylogenetically
      sound given the conservation of this dual function in the Drp1 family. No direct
      experimental evidence in C. elegans, but strong inference from ortholog function.
    supported_by:
    - reference_id: file:worm/drp-1/drp-1-deep-research-falcon.md
      supporting_text: DRP-1 catalyzes mitochondrial (and peroxisomal, by inference)
        fission by binding the outer mitochondrial membrane (OMM), oligomerizing,
        and coupling GTP hydrolysis to membrane constriction and scission
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: DRP-1 localizes to mitochondria at fission sites. DRP-1::GFP is observed
      in spots on mitochondria where scission occurs (PMID:10619028).
    action: ACCEPT
    reason: Well-supported by experimental evidence. DRP-1 is recruited to mitochondria
      to execute its fission function.
    supported_by:
    - reference_id: PMID:10619028
      supporting_text: DRP-1 fused to GFP is observed in spots on mitochondria where
        scission eventually occurs.
- term:
    id: GO:0005874
    label: microtubule
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: This annotation appears to be inherited from classical dynamin family
      members that associate with microtubules for endocytic vesicle transport. While
      dynamin superfamily members can associate with microtubules, there is no direct
      evidence for DRP-1 microtubule localization in C. elegans.
    action: MARK_AS_OVER_ANNOTATED
    reason: This annotation likely derives from phylogenetic inference across the
      broader dynamin family, but DRP-1/Drp1 subfamily proteins function at mitochondria
      and peroxisomes, not at the plasma membrane or in endocytic trafficking where
      microtubule association is relevant. No C. elegans-specific evidence supports
      this localization for drp-1.
- term:
    id: GO:0008017
    label: microtubule binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Similar to the microtubule localization annotation, this molecular function
      annotation appears to derive from classical dynamins rather than the DRP1 subfamily.
      There is no evidence that DRP-1 binds microtubules in C. elegans.
    action: MARK_AS_OVER_ANNOTATED
    reason: The DRP-1/Drp1 subfamily is functionally distinct from classical dynamins
      that operate in endocytosis and require microtubule binding. DRP-1's function
      at mitochondria and peroxisomes does not require microtubule binding. This annotation
      represents over-inference from the broader dynamin family.
- term:
    id: GO:0000166
    label: nucleotide binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: DRP-1 binds GTP as part of its GTPase activity. The protein has conserved
      G1-G5 motifs for nucleotide binding in its dynamin-type G domain.
    action: ACCEPT
    reason: This is a parent term of the more specific GTP binding annotation. While
      somewhat redundant given the GTP binding annotation, it is not incorrect. The
      IEA annotation from UniProt keyword mapping is appropriate.
- term:
    id: GO:0003924
    label: GTPase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: GTPase activity is the core catalytic function. This IEA annotation from
      InterPro domain mapping is consistent with the IBA annotation.
    action: ACCEPT
    reason: Duplicates the IBA annotation but via a different evidence pathway (InterPro
      domain mapping). Both are valid and consistent.
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: GTP binding is required for DRP-1 GTPase activity and membrane fission
      function. The G1-G5 motifs in the dynamin-type G domain mediate GTP binding.
    action: ACCEPT
    reason: Well-supported by domain architecture. GTP binding is an intrinsic property
      of the conserved dynamin GTPase domain.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Cytoplasmic localization is consistent with experimental evidence showing
      DRP-1 in cytosol before recruitment to mitochondria.
    action: ACCEPT
    reason: Consistent with experimental observations. DRP-1 exists in cytosolic pools.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: Mitochondrial localization is well-supported by experimental evidence
      showing DRP-1::GFP at mitochondrial fission sites (PMID:10619028).
    action: ACCEPT
    reason: Consistent with experimental evidence for DRP-1 localization to mitochondria.
- term:
    id: GO:0005741
    label: mitochondrial outer membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: DRP-1 functions at the mitochondrial outer membrane where it mediates
      membrane scission. The protein is recruited to the OMM at constriction sites.
    action: ACCEPT
    reason: Well-supported by experimental evidence. DRP-1 controls scission of the
      mitochondrial outer membrane specifically (PMID:10619028).
    supported_by:
    - reference_id: PMID:10619028
      supporting_text: wild-type DRP-1 contributes to the final stages of mitochondrial
        division by controlling scission of the mitochondrial outer membrane.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: DRP-1 resides in the cytosol and is recruited to mitochondria upon fission
      signals. UniProt subcellular location annotation supports cytosol localization.
    action: ACCEPT
    reason: Consistent with experimental evidence that DRP-1 exists in cytosolic pools
      before recruitment to mitochondria (PMID:21949250).
- term:
    id: GO:0006915
    label: apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: DRP-1 has a role in apoptosis, promoting mitochondrial fragmentation
      and elimination during cell death. However, drp-1 is not required for apoptosis
      activation but acts downstream of caspase CED-3 in cell death execution (PMID:18722182).
    action: KEEP_AS_NON_CORE
    reason: The apoptotic role is real but secondary to the core mitochondrial fission
      function. DRP-1 acts downstream of CED-3 to promote mitochondrial elimination
      in dying cells, but is not essential for apoptosis activation. The annotation
      is appropriate but represents a context-dependent function rather than core
      function.
    supported_by:
    - reference_id: PMID:18722182
      supporting_text: drp-1 and fis-2 function independent of one another and the
        Bcl-2 homolog CED-9 and downstream of the CED-3 caspase to promote elimination
        of mitochondria in dying cells
- term:
    id: GO:0008289
    label: lipid binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: Dynamin-related proteins bind membrane lipids as part of their membrane
      remodeling function. The annotation is based on UniProt lipid-binding keyword.
    action: ACCEPT
    reason: Membrane binding is required for DRP-1 function. GTPase activity is increased
      by binding to phospholipid membranes (UniProt activity regulation note). Cross-species
      studies show Drp1 binds membranes via adaptors and lipid interactions.
- term:
    id: GO:0016787
    label: hydrolase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: DRP-1 is a GTPase that hydrolyzes GTP to GDP + Pi. Hydrolase activity
      is a parent term of GTPase activity.
    action: ACCEPT
    reason: True but very general. GTPase activity is a more informative child term
      that is also annotated. This parent term is not wrong.
- term:
    id: GO:0000266
    label: mitochondrial fission
  evidence_type: IMP
  original_reference_id: PMID:19327994
  review:
    summary: This study examined drp-1 mutants and found mitochondrial fission is
      defective. The study specifically looked at mitochondrial morphology in drp-1
      mutants in the context of analyzing Bcl-2 protein function.
    action: ACCEPT
    reason: Direct experimental evidence. The study confirms drp-1 mutants have defective
      mitochondrial fission while fusion still occurs, resulting in abnormal mitochondrial
      connectivity.
    supported_by:
    - reference_id: PMID:19327994
      supporting_text: in a drp-1 mutant, in which mitochondrial fusion occurs but
        mitochondrial fission is defective
- term:
    id: GO:0000266
    label: mitochondrial fission
  evidence_type: IGI
  original_reference_id: PMID:18827010
  review:
    summary: This study showed genetic interaction between drp-1 and ced-9 in regulating
      mitochondrial morphology. Increased DRP-1 expression suppresses the interconnected
      mitochondria phenotype caused by CED-9 overexpression.
    action: ACCEPT
    reason: Valid genetic interaction evidence. The study demonstrates DRP-1 functions
      in opposition to CED-9 in controlling mitochondrial morphology, with DRP-1 promoting
      fission.
    supported_by:
    - reference_id: PMID:18827010
      supporting_text: This mitochondrial phenotype is partially suppressed by increased
        expression of the dynamin-related GTPase DRP-1
- term:
    id: GO:0000266
    label: mitochondrial fission
  evidence_type: IMP
  original_reference_id: PMID:18827010
  review:
    summary: The study examines drp-1 function in mitochondrial dynamics and shows
      it promotes fission. DRP-1 overexpression causes fragmented mitochondria.
    action: ACCEPT
    reason: Direct mutant phenotype evidence supporting DRP-1 role in mitochondrial
      fission.
    supported_by:
    - reference_id: PMID:18827010
      supporting_text: This mitochondrial phenotype is partially suppressed by increased
        expression of the dynamin-related GTPase DRP-1
- term:
    id: GO:0009792
    label: embryo development ending in birth or egg hatching
  evidence_type: IMP
  original_reference_id: PMID:10619028
  review:
    summary: RNAi knockdown of drp-1 causes embryonic lethality. This represents a
      broad developmental phenotype resulting from the essential mitochondrial fission
      function.
    action: KEEP_AS_NON_CORE
    reason: The embryonic lethality phenotype is real but represents a pleiotropic
      consequence of disrupted mitochondrial dynamics rather than a specific developmental
      function. DRP-1's role is in mitochondrial fission; the developmental phenotype
      is downstream of this core function.
    supported_by:
    - reference_id: PMID:10619028
      supporting_text: mitochondria are disrupted by mutations in a C. elegans dynamin-related
        protein (DRP-1).
      full_text_unavailable: true
- term:
    id: GO:0006915
    label: apoptotic process
  evidence_type: IGI
  original_reference_id: PMID:18722182
  review:
    summary: This study demonstrated genetic interaction between drp-1 and ced-3 (caspase)
      in apoptosis. DRP-1 functions downstream of CED-3 to promote cell death execution
      through mitochondrial elimination.
    action: KEEP_AS_NON_CORE
    reason: The apoptotic role is real but represents a secondary function. DRP-1
      is not required for apoptosis activation but acts downstream of caspase to facilitate
      mitochondrial elimination in dying cells. The annotation is correct but this
      is not the core function.
    supported_by:
    - reference_id: PMID:18722182
      supporting_text: drp-1 and fis-2 function independent of one another and the
        Bcl-2 homolog CED-9 and downstream of the CED-3 caspase to promote elimination
        of mitochondria in dying cells
- term:
    id: GO:0000266
    label: mitochondrial fission
  evidence_type: IMP
  original_reference_id: PMID:10619028
  review:
    summary: This is the foundational paper establishing DRP-1 function in mitochondrial
      fission. Mutant DRP-1 causes mitochondrial matrix to retract into blebs connected
      by outer membrane tubules, indicating outer membrane scission is inhibited.
      Overexpression causes excessive fragmentation.
    action: ACCEPT
    reason: Primary experimental evidence establishing DRP-1 as a mitochondrial fission
      factor. This is the core function of the protein.
    supported_by:
    - reference_id: PMID:10619028
      supporting_text: Mutant DRP-1 causes the mitochondrial matrix to retract into
        large blebs that are both surrounded and connected by tubules of outer membrane.
        This indicates that scission of the mitochondrial outer membrane is inhibited
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: ISS
  original_reference_id: PMID:10619028
  review:
    summary: GTP binding is inferred by sequence similarity to mammalian DRP1 (UniProtKB:O00429).
      The conserved dynamin-type G domain with G1-G5 motifs supports this function.
    action: ACCEPT
    reason: Valid sequence similarity-based inference. The conserved domain architecture
      strongly supports GTP binding function.
    supported_by:
    - reference_id: PMID:10619028
      supporting_text: C. elegans dynamin-related protein (DRP-1)
      full_text_unavailable: true
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: PMID:10619028
  review:
    summary: Direct experimental evidence showing DRP-1::GFP localization to mitochondria
      at fission sites.
    action: ACCEPT
    reason: Strong experimental evidence. GFP-tagged DRP-1 was observed at sites of
      mitochondrial scission.
    supported_by:
    - reference_id: PMID:10619028
      supporting_text: DRP-1 fused to GFP is observed in spots on mitochondria where
        scission eventually occurs.
- term:
    id: GO:0008637
    label: apoptotic mitochondrial changes
  evidence_type: IMP
  original_reference_id: PMID:15716954
  review:
    summary: This study showed DRP-1 is required for mitochondrial fragmentation during
      EGL-1-induced cell death. DRP-1 overexpression is sufficient to induce mitochondrial
      fragmentation and cell death.
    action: ACCEPT
    reason: Well-supported by experimental evidence. DRP-1 mediates mitochondrial
      fragmentation during apoptosis, which represents apoptotic mitochondrial changes.
    supported_by:
    - reference_id: PMID:15716954
      supporting_text: DRP-1/dynamin-related protein, a key component of the mitochondrial
        fission machinery, is required and sufficient to induce mitochondrial fragmentation
        and programmed cell death during C. elegans development.
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:
  - statement: IBA annotations based on PANTHER phylogenetic trees with characterized
      orthologs
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10619028
  title: C. elegans dynamin-related protein DRP-1 controls severing of the mitochondrial
    outer membrane.
  findings:
  - statement: Established DRP-1 as the mitochondrial fission factor in C. elegans
    supporting_text: wild-type DRP-1 contributes to the final stages of mitochondrial
      division by controlling scission of the mitochondrial outer membrane.
  - statement: Mutant DRP-1 inhibits outer membrane scission while inner membrane
      scission still occurs
    supporting_text: Mutant DRP-1 causes the mitochondrial matrix to retract into
      large blebs that are both surrounded and connected by tubules of outer membrane.
  - statement: DRP-1::GFP localizes to sites of mitochondrial scission
    supporting_text: DRP-1 fused to GFP is observed in spots on mitochondria where
      scission eventually occurs.
  - statement: Overexpression causes excessive mitochondrial fragmentation
    supporting_text: Overexpressed wild-type DRP-1 causes mitochondria to become excessively
      fragmented
- id: PMID:15716954
  title: DRP-1-mediated mitochondrial fragmentation during EGL-1-induced cell death
    in C. elegans.
  findings:
  - statement: DRP-1 is required and sufficient to induce mitochondrial fragmentation
      during apoptosis
    supporting_text: DRP-1/dynamin-related protein, a key component of the mitochondrial
      fission machinery, is required and sufficient to induce mitochondrial fragmentation
      and programmed cell death during C. elegans development.
  - statement: Mitochondrial fragmentation is induced by EGL-1 and blocked by ced-9
      mutations
    supporting_text: Mitochondrial fragmentation is induced by the BH3-only protein
      EGL-1 and can be blocked by mutations in the bcl-2-like gene ced-9
  - statement: Mitochondrial fragmentation is independent of CED-4 and CED-3
    supporting_text: Mitochondrial fragmentation is independent of CED-4/Apaf-1 and
      CED-3/caspase
- id: PMID:18722182
  title: Caenorhabditis elegans drp-1 and fis-2 regulate distinct cell-death execution
    pathways downstream of ced-3 and independent of ced-9.
  findings:
  - statement: drp-1 is not required for apoptosis activation but acts downstream
      of CED-3
    supporting_text: profusion genes fzo-1 and eat-3 or the profission gene drp-1
      are not required for apoptosis activation in C. elegans.
  - statement: DRP-1 promotes mitochondrial elimination in dying cells
    supporting_text: drp-1 and fis-2 function independent of one another and the Bcl-2
      homolog CED-9 and downstream of the CED-3 caspase to promote elimination of
      mitochondria in dying cells
  - statement: CED-3 cleaves DRP-1; this cleavage is required for pro-apoptotic but
      not fission function
    supporting_text: CED-3 can cleave DRP-1, which appears to be important for DRP-1's
      proapoptotic function, but not its mitochondria fission function.
- id: PMID:18827010
  title: CED-9 and mitochondrial homeostasis in C. elegans muscle.
  findings:
  - statement: CED-9 overexpression causes interconnected mitochondria
    supporting_text: increased CED-9 expression in these cells produces highly interconnected
      mitochondria.
  - statement: DRP-1 overexpression suppresses CED-9-induced mitochondrial connectivity
    supporting_text: This mitochondrial phenotype is partially suppressed by increased
      expression of the dynamin-related GTPase DRP-1
- id: PMID:19327994
  title: Bcl-2 proteins EGL-1 and CED-9 do not regulate mitochondrial fission or fusion
    in Caenorhabditis elegans.
  findings:
  - statement: drp-1 mutants have defective fission with normal fusion
    supporting_text: in a drp-1 mutant, in which mitochondrial fusion occurs but mitochondrial
      fission is defective
  - statement: EGL-1 and CED-9 do not regulate mitochondrial fission or fusion
    supporting_text: loss of egl-1 or ced-9, or overexpression of their gene products,
      had no apparent effect on mitochondrial connectivity or mitochondrial size.
- id: PMID:21463460
  title: The dynamin-related protein DRP-1 and the insulin signaling pathway cooperate
    to modulate Caenorhabditis elegans longevity.
  findings: []
- id: PMID:21949250
  title: A molecular switch that governs mitochondrial fusion and fission mediated
    by the BCL2-like protein CED-9 of Caenorhabditis elegans.
  findings:
  - statement: DRP-1 interacts with CED-9
    supporting_text: CED-9 also physically interacts with the mitochondrial fission
      protein DRP-1
  - statement: Interaction is enhanced by GTP rather than GDP
    supporting_text: this interaction can be enhanced when CED-9 is associated with
      the BH3-only protein EGL-1.
  - statement: DRP-1 is recruited to mitochondria by CED-9/EGL-1 complex
    supporting_text: the EGL-1-CED-9 complex promotes mitochondrial fission by recruiting
      DRP-1 to mitochondria
- id: PMID:33734301
  title: Autophagy facilitates mitochondrial rebuilding after acute heat stress via
    a DRP-1-dependent process.
  findings: []
- id: file:worm/drp-1/drp-1-deep-research-falcon.md
  title: Deep research summary for drp-1
  findings:
  - statement: DRP-1 is recruited from cytosol to OMM by adaptor proteins including
      FIS-1, FIS-2 and MFF-1/MFF-2
  - statement: Loss of drp-1 in dystrophin mutants reduces TUNEL-positive muscle cells
      from 5.28 to 2.07 per animal
  - statement: drp-1 disruption during development extends daf-2 (IIS) mutant longevity
core_functions:
- description: DRP-1 is a dynamin-related GTPase that controls mitochondrial outer
    membrane fission. It is recruited from the cytosol to the mitochondrial outer
    membrane at constriction sites, where it oligomerizes and uses GTP hydrolysis
    to drive membrane scission.
  molecular_function:
    id: GO:0003924
    label: GTPase activity
  directly_involved_in:
  - id: GO:0000266
    label: mitochondrial fission
  locations:
  - id: GO:0005741
    label: mitochondrial outer membrane
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: PMID:10619028
    supporting_text: wild-type DRP-1 contributes to the final stages of mitochondrial
      division by controlling scission of the mitochondrial outer membrane.
proposed_new_terms: []
suggested_questions:
- question: Does C. elegans DRP-1 directly mediate peroxisome fission, or is this
    function performed by a different dynamin-related protein?
- question: What are the specific adaptor proteins that recruit DRP-1 to the mitochondrial
    outer membrane in C. elegans?
- question: How does post-translational modification (e.g., phosphorylation, sumoylation)
    regulate DRP-1 activity in worms?
suggested_experiments:
- description: Direct visualization of DRP-1 at peroxisomes to confirm peroxisome
    fission function
- description: Biochemical characterization of C. elegans DRP-1 GTPase activity and
    membrane binding properties
- description: Identification of the CED-3 cleavage products and their functional
    differences
tags:
- caeel-mitophagy

drp-1

Gene Description

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Core Functions

DRP-1 is a dynamin-related GTPase that controls mitochondrial outer membrane fission. It is recruited from the cytosol to the mitochondrial outer membrane at constriction sites, where it oligomerizes and uses GTP hydrolysis to drive membrane scission.

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