eat-3

Summary: EAT-3 retains the dynamin-family GTP-binding and hydrolytic mechanism underlying mitochondrial membrane remodeling.

Reason: The GTPase IBD is at PTN000170013 in PTHR11566. EAT-3 has conserved nucleotide-binding motifs, and primary mutations and intragenic suppressors in its GTPase domain alter and restore biological function (PMID:18454199). Those suppressor experiments are genetic, not direct measurements of rescued enzyme activity; the authors propose restoration of GTP interaction or hydrolysis-associated conformational changes. Broad nucleotide binding and hydrolase annotations remain valid alongside GTPase specificity.

Summary: Cytoplasm is an accurate broad compartment for a mitochondrial protein.

Reason: The PTN000170013 cytoplasm IBD does not imply free cytosolic localization. Mitochondria are cytoplasmic organelles, so the experimentally supported mitochondrial and intermembrane-space localizations are compatible with this broad term. The previous objection conflated cytoplasm with cytosol.

Summary: EAT-3 functions at the mitochondrial inner membrane with a domain exposed to the intermembrane space.

Reason: The fusion/membrane/IMS IBD is at PTN007514526 in PTHR11566. Target genetic and ultrastructural experiments demonstrate disrupted fusion and cristae organization (PMID:18454199), while fractionation and protease protection use EAT-3 as an inner-membrane/IMS marker (PMID:21248201). Target fusion evidence contributing to the PAINT node is legitimate descendant grounding, not circularity. The broader mitochondrial-membrane term remains correct.

Summary: EAT-3 functions at the mitochondrial inner membrane with a domain exposed to the intermembrane space.

Reason: The fusion/membrane/IMS IBD is at PTN007514526 in PTHR11566. Target genetic and ultrastructural experiments demonstrate disrupted fusion and cristae organization (PMID:18454199), while fractionation and protease protection use EAT-3 as an inner-membrane/IMS marker (PMID:21248201). Target fusion evidence contributing to the PAINT node is legitimate descendant grounding, not circularity. The broader mitochondrial-membrane term remains correct.

Summary: The inherited nonmitochondrial function requires assessment beyond the dominant inner-membrane role.

Reason: The GOA assertion traces to PTN008520527 in PTHR11566. Primary experiments establish mitochondrial targeting, protease-protected localization, inner-membrane fusion and cristae organization. These findings create a mechanistic question about access to cytosolic microtubules or peroxisomes, but do not alone exclude every precursor, processed form or additional context. The previous rejection relied on principal localization and family specialization without resolving inheritance or loss at the relevant ancestral node. Keep the exact inherited claim unresolved after the focused source/target report. The report confirms that PTN000170013 and PTN008520527 are ancestors of OPA1 node PTN007514526, so donor specialization alone does not overturn the ancestral placement. Its missing PH/PRD/GED-domain argument is not a demonstrated requirement for every microtubule interaction or membrane-remodeling mechanism. Rejection does not require a negative capacity assay. Here the ancestry is verified and the proposed domain-loss premise is contradicted; topology remains a strong mechanistic constraint requiring adjudication of inheritance or loss. PMID:32228866 explicitly identifies human OPA1 middle/GED stalk architecture (Fig. 1A and Fig. 3); the report's claimed absence of GED is therefore not a valid family-level premise. This ortholog structure does not itself demonstrate the disputed EAT-3 capacity.

Summary: EAT-3 functions at the mitochondrial inner membrane with a domain exposed to the intermembrane space.

Reason: The fusion/membrane/IMS IBD is at PTN007514526 in PTHR11566. Target genetic and ultrastructural experiments demonstrate disrupted fusion and cristae organization (PMID:18454199), while fractionation and protease protection use EAT-3 as an inner-membrane/IMS marker (PMID:21248201). Target fusion evidence contributing to the PAINT node is legitimate descendant grounding, not circularity. The broader mitochondrial-membrane term remains correct.

Summary: The inherited nonmitochondrial function requires assessment beyond the dominant inner-membrane role.

Reason: The GOA assertion traces to PTN000170013 in PTHR11566. Primary experiments establish mitochondrial targeting, protease-protected localization, inner-membrane fusion and cristae organization. These findings create a mechanistic question about access to cytosolic microtubules or peroxisomes, but do not alone exclude every precursor, processed form or additional context. The previous rejection relied on principal localization and family specialization without resolving inheritance or loss at the relevant ancestral node. Keep the exact inherited claim unresolved after the focused source/target report. The report confirms that PTN000170013 and PTN008520527 are ancestors of OPA1 node PTN007514526, so donor specialization alone does not overturn the ancestral placement. Its missing PH/PRD/GED-domain argument is not a demonstrated requirement for every microtubule interaction or membrane-remodeling mechanism. Rejection does not require a negative capacity assay. Here the ancestry is verified and the proposed domain-loss premise is contradicted; topology remains a strong mechanistic constraint requiring adjudication of inheritance or loss. PMID:32228866 explicitly identifies human OPA1 middle/GED stalk architecture (Fig. 1A and Fig. 3); the report's claimed absence of GED is therefore not a valid family-level premise. This ortholog structure does not itself demonstrate the disputed EAT-3 capacity.

Summary: The inherited nonmitochondrial function requires assessment beyond the dominant inner-membrane role.

Reason: The GOA assertion traces to PTN000170013 in PTHR11566. Primary experiments establish mitochondrial targeting, protease-protected localization, inner-membrane fusion and cristae organization. These findings create a mechanistic question about access to cytosolic microtubules or peroxisomes, but do not alone exclude every precursor, processed form or additional context. The previous rejection relied on principal localization and family specialization without resolving inheritance or loss at the relevant ancestral node. Keep the exact inherited claim unresolved after the focused source/target report. The report confirms that PTN000170013 and PTN008520527 are ancestors of OPA1 node PTN007514526, so donor specialization alone does not overturn the ancestral placement. Its missing PH/PRD/GED-domain argument is not a demonstrated requirement for every microtubule interaction or membrane-remodeling mechanism. Rejection does not require a negative capacity assay. Here the ancestry is verified and the proposed domain-loss premise is contradicted; topology remains a strong mechanistic constraint requiring adjudication of inheritance or loss. PMID:32228866 explicitly identifies human OPA1 middle/GED stalk architecture (Fig. 1A and Fig. 3); the report's claimed absence of GED is therefore not a valid family-level premise. This ortholog structure does not itself demonstrate the disputed EAT-3 capacity.

Summary: EAT-3 retains the dynamin-family GTP-binding and hydrolytic mechanism underlying mitochondrial membrane remodeling.

Reason: The GTPase IBD is at PTN000170013 in PTHR11566. EAT-3 has conserved nucleotide-binding motifs, and primary mutations and intragenic suppressors in its GTPase domain alter and restore biological function (PMID:18454199). Those suppressor experiments are genetic, not direct measurements of rescued enzyme activity; the authors propose restoration of GTP interaction or hydrolysis-associated conformational changes. Broad nucleotide binding and hydrolase annotations remain valid alongside GTPase specificity.

Summary: EAT-3 retains the dynamin-family GTP-binding and hydrolytic mechanism underlying mitochondrial membrane remodeling.

Reason: The GTPase IBD is at PTN000170013 in PTHR11566. EAT-3 has conserved nucleotide-binding motifs, and primary mutations and intragenic suppressors in its GTPase domain alter and restore biological function (PMID:18454199). Those suppressor experiments are genetic, not direct measurements of rescued enzyme activity; the authors propose restoration of GTP interaction or hydrolysis-associated conformational changes. Broad nucleotide binding and hydrolase annotations remain valid alongside GTPase specificity.

Summary: EAT-3 retains the dynamin-family GTP-binding and hydrolytic mechanism underlying mitochondrial membrane remodeling.

Reason: The GTPase IBD is at PTN000170013 in PTHR11566. EAT-3 has conserved nucleotide-binding motifs, and primary mutations and intragenic suppressors in its GTPase domain alter and restore biological function (PMID:18454199). Those suppressor experiments are genetic, not direct measurements of rescued enzyme activity; the authors propose restoration of GTP interaction or hydrolysis-associated conformational changes. Broad nucleotide binding and hydrolase annotations remain valid alongside GTPase specificity.

Summary: EAT-3 functions at the mitochondrial inner membrane with a domain exposed to the intermembrane space.

Reason: The fusion/membrane/IMS IBD is at PTN007514526 in PTHR11566. Target genetic and ultrastructural experiments demonstrate disrupted fusion and cristae organization (PMID:18454199), while fractionation and protease protection use EAT-3 as an inner-membrane/IMS marker (PMID:21248201). Target fusion evidence contributing to the PAINT node is legitimate descendant grounding, not circularity. The broader mitochondrial-membrane term remains correct.

Summary: EAT-3 functions at the mitochondrial inner membrane with a domain exposed to the intermembrane space.

Reason: The fusion/membrane/IMS IBD is at PTN007514526 in PTHR11566. Target genetic and ultrastructural experiments demonstrate disrupted fusion and cristae organization (PMID:18454199), while fractionation and protease protection use EAT-3 as an inner-membrane/IMS marker (PMID:21248201). Target fusion evidence contributing to the PAINT node is legitimate descendant grounding, not circularity. The broader mitochondrial-membrane term remains correct.

Summary: Direct C. elegans assays argue against transferring the canonical OPA1 apoptotic role to EAT-3.

Reason: This decision rests on experiments, not absence of target publications or mitochondrial specialization. PMID:18454199 finds no increase in dying embryonic cells and no rescue of growth or brood-size defects by ced-3/ced-4 loss. PMID:18722182 additionally tests developmental cell-corpse profiles, inappropriate pharyngeal-cell survival and a sensitized ced-3 background without detecting an eat-3-dependent death effect. These data oppose the inherited canonical apoptotic role represented by the keyword mapping, while not proving that EAT-3 can never affect death under any untested stress.

Summary: Lipid interaction is a supported family mechanism of OPA1/Mgm1-type membrane remodeling.

Reason: Retain this inferred EAT-3 lipid-binding activity while clearly distinguishing ortholog biochemistry from direct worm assays. PMID:19703904 maps lipid-binding determinants in yeast Mgm1 using liposome association, activity and complementation experiments; PMID:28628083 reconstitutes human OPA1-cardiolipin fusion. These are relevant support for conservation of the broad function. The old added PMID:23226476 instead concerns hCG-driven mouse reproductive dysfunction and tumorigenesis, and is withdrawn as a wrong supporting identifier.

Summary: EAT-3 retains the dynamin-family GTP-binding and hydrolytic mechanism underlying mitochondrial membrane remodeling.

Reason: The GTPase IBD is at PTN000170013 in PTHR11566. EAT-3 has conserved nucleotide-binding motifs, and primary mutations and intragenic suppressors in its GTPase domain alter and restore biological function (PMID:18454199). Those suppressor experiments are genetic, not direct measurements of rescued enzyme activity; the authors propose restoration of GTP interaction or hydrolysis-associated conformational changes. Broad nucleotide binding and hydrolase annotations remain valid alongside GTPase specificity.

Summary: EAT-3 is experimentally recovered in the mitochondrial fraction.

Reason: Although the paper foregrounds MOMA-1, PMID:21248201 explicitly assays EAT-3 as a compartment control: 88% is in the mitochondrial pellet, and it is protected from protease in intact mitochondria. This is direct evidence on EAT-3, not a citation misattributed from the protein named in the title.

Summary: eat-3 mutants have slow development and growth defects. This is a phenotypic consequence of mitochondrial dysfunction rather than a core function.

Reason: While eat-3 mutants do have developmental defects (slow growth, delayed development), these are secondary consequences of impaired mitochondrial function rather than a direct role in development. The core function is mitochondrial inner membrane fusion.

Summary: eat-3 mutants show growth defects, but this is a pleiotropic consequence of mitochondrial dysfunction rather than a direct regulatory role in growth.

Reason: eat-3 loss of function causes slow growth and small body size, but this is due to impaired mitochondrial function (oxidative phosphorylation defects) rather than a direct role in regulating organismal growth. The growth defects are consistent with metabolic insufficiency.

Summary: This is a duplicate annotation with IGI evidence, showing genetic interactions affecting growth. Same reasoning as above - secondary phenotype.

Reason: Growth phenotype is a secondary consequence of mitochondrial dysfunction, not a core regulatory function.

Summary: The cell-death study directly examines mitochondrial fusion phenotypes in eat-3 mutants.

Reason: PMID:18722182 includes mitochondrial staining and electron microscopy of eat-3(ad426) and eat-3(tm1107) embryos. Fragmentation and altered cristae independently support the fusion annotation; the abstract focus on apoptosis does not weaken these full-text target experiments.

Summary: eat-3 mutants are hypersensitive to paraquat and show induction of SOD-2. This is a stress response consequence of mitochondrial dysfunction.

Reason: eat-3 mutants show hypersensitivity to paraquat (superoxide) and compensatory induction of SOD-2, but this is a consequence of mitochondrial dysfunction leading to increased ROS production, not a primary function in oxidative stress response.

Summary: EAT-3 promotes mitochondrial inner-membrane fusion and maintains cristae architecture.

Reason: PMID:18454199 combines target genetics, rescue and electron microscopy: mutant mitochondria fragment, contain inner-membrane septae and have reduced cristae. The phenotype and conserved OPA1/Mgm1 mechanism support direct membrane-organization work rather than only an upstream requirement for mitochondrial health. No respiratory-chain catalytic activity is inferred.

Summary: EAT-3 promotes mitochondrial inner-membrane fusion and maintains cristae architecture.

Reason: PMID:18454199 combines target genetics, rescue and electron microscopy: mutant mitochondria fragment, contain inner-membrane septae and have reduced cristae. The phenotype and conserved OPA1/Mgm1 mechanism support direct membrane-organization work rather than only an upstream requirement for mitochondrial health. No respiratory-chain catalytic activity is inferred.

Summary: eat-3 mutants show reduced body size and growth, a consequence of mitochondrial dysfunction.

Reason: Growth defects are a secondary phenotype of mitochondrial dysfunction, not a core function of EAT-3.