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.
| 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. |
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Download this section (compressed HTML)Q: Does C. elegans DRP-1 directly mediate peroxisome fission, or is this function performed by a different dynamin-related protein?
Q: What are the specific adaptor proteins that recruit DRP-1 to the mitochondrial outer membrane in C. elegans?
Q: How does post-translational modification (e.g., phosphorylation, sumoylation) regulate DRP-1 activity in worms?
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
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