ACO1 encodes the major aconitase (aconitate hydratase, EC 4.2.1.3) of Saccharomyces cerevisiae, a [4Fe-4S] cluster enzyme of the aconitase/IPM isomerase family that interconverts citrate and D-threo-isocitrate via cis-aconitate. Most of the protein is imported into the mitochondrial matrix, where it catalyses the second step of the tricarboxylic acid cycle; aco1 null mutants are glutamate auxotrophs and cannot grow on non-fermentable carbon sources. A small cytosolic pool (about 6%) derived from the same translation product supplies the isocitrate needed by the cytosolic glyoxylate shunt. ACO1 also makes a minor contribution to the homocitrate-to-homoaconitate step of lysine biosynthesis, a reaction handled mainly by its paralog ACO2. Independently of catalysis, Aco1p is a component of mitochondrial nucleoids, binds single- and double-stranded DNA and is required for mitochondrial DNA maintenance.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003690 double-stranded DNA binding | IDA PMID:17698960 Yeast aconitase binds and provides metabolically coupled pro... | KEEP AS NON CORE | Summary: Chen et al. showed recombinant/purified Aco1p binds double-stranded DNA (GC preference) and protects mtDNA from point mutations and ssDNA breaks; this is the nucleoid-associated moonlighting role, separable from catalysis. Reason: Direct binding evidence; real but secondary to the TCA-cycle enzymatic role. Supporting Evidence: PMID:17698960 Aconitase binds to both ds- and ssDNA, with a preference for GC-containing sequences. PMID:15692048 We show that this Krebs-cycle enzyme is essential for mtDNA maintenance independent of its catalytic activity. |
| GO:0003697 single-stranded DNA binding | IDA PMID:17698960 Yeast aconitase binds and provides metabolically coupled pro... | KEEP AS NON CORE | Summary: Same study (PMID:17698960) showed Aco1p also binds single-stranded DNA, consistent with protection of mtDNA from ssDNA breaks within nucleoids. Reason: Direct binding evidence for the mtDNA-maintenance moonlighting role; non-core. Supporting Evidence: PMID:17698960 Aconitase binds to both ds- and ssDNA, with a preference for GC-containing sequences. |
| GO:0003729 mRNA binding | IDA PMID:18959479 Diverse RNA-binding proteins interact with functionally rela... | KEEP AS NON CORE | Summary: RIP-chip survey of candidate RNA-binding proteins (Hogan et al. 2008) found Aco1 selectively associated with transcripts of the mitochondrial genome. Large-scale association data; no follow-up showing a regulatory role in yeast (unlike mammalian IRP1/cytosolic aconitase). Reason: Experimental association, plausibly reflecting nucleoid proximity; keep as non-core. Supporting Evidence: PMID:18959479 selectively binds transcripts encoded by the mitochondrial genome |
| GO:0003994 aconitate hydratase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA on the PTN000186533 mitochondrial-type aconitase node; ACO1 is the canonical yeast mitochondrial aconitase and also has its own direct assay (PMID:1972545), so the inherited function is well grounded. Reason: Core catalytic activity, consistent with direct evidence. Supporting Evidence: file:yeast/ACO1/ACO1-uniprot.txt Reaction=citrate = D-threo-isocitrate; Xref=Rhea:RHEA:10336, PMID:1972545 Identification of the aconitase gene was established by enzymatic assays and molecular analyses. |
| GO:0003994 aconitate hydratase activity | IDA PMID:1972545 Molecular cloning of the yeast mitochondrial aconitase gene ... | ACCEPT | Summary: Gangloff et al. cloned ACO1 by complementing the aconitase-deficient glu1-1 strain and confirmed identity by enzymatic assays; this is the defining biochemical evidence for the activity. Reason: Direct experimental evidence of aconitate hydratase activity. Supporting Evidence: PMID:1972545 Identification of the aconitase gene was established by enzymatic assays and molecular analyses. file:yeast/ACO1/ACO1-uniprot.txt Reaction=citrate = D-threo-isocitrate; Xref=Rhea:RHEA:10336, |
| GO:0003994 aconitate hydratase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (InterPro IPR006248 mitochondrial-like aconitase, Rhea:10336, EC 4.2.1.3) transferring aconitate hydratase activity; correct for ACO1. Reason: Correct electronic assignment of the core activity. Supporting Evidence: file:yeast/ACO1/ACO1-uniprot.txt Reaction=citrate = D-threo-isocitrate; Xref=Rhea:RHEA:10336, |
| GO:0003994 aconitate hydratase activity | IMP PMID:1972545 Molecular cloning of the yeast mitochondrial aconitase gene ... | ACCEPT | Summary: Disruption of ACO1 abolished aconitase function, giving glutamate auxotrophy (no isocitrate/2-oxoglutarate for glutamate synthesis). Reason: Mutant phenotype consistent with loss of the catalytic activity. Supporting Evidence: PMID:1972545 Disruption of the gene by deletion-insertion led to glutamate auxotrophy. |
| GO:0003994 aconitate hydratase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA from the glyoxylate cycle (GLYOXYLATE-BYPASS). ACO1 is the only aconitase shown to supply the cytosolic glyoxylate shunt (cytosolic Aco1p pool), so the activity assignment in this pathway context is supported. Reason: Correct activity; pathway role experimentally supported by PMID:15975908. Supporting Evidence: PMID:15975908 Together, our data indicate that yeast aconitase isoenzymes distribute between two distinct subcellular compartments and participate in two separate metabolic pathways; the glyoxylate shunt in the cytosol and the TCA cycle in mitochondria. |
| GO:0003994 aconitate hydratase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA from the TCA/glyoxylate superpathway (PWY3O-94) assigning aconitate hydratase activity; correct for ACO1. Reason: Correct activity class. Supporting Evidence: file:yeast/ACO1/ACO1-uniprot.txt Reaction=citrate = D-threo-isocitrate; Xref=Rhea:RHEA:10336, |
| GO:0003994 aconitate hydratase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA from the eukaryotic TCA cycle pathway (TCA-EUK-PWY); ACO1 is the TCA-cycle aconitase. Reason: Correct activity in the correct pathway. Supporting Evidence: file:yeast/ACO1/ACO1-uniprot.txt Catalyzes the isomerization of citrate to isocitrate via cis- |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping to cytoplasm; reflects the documented small cytosolic Aco1p pool (~6%) that serves the glyoxylate shunt. Reason: Supported by direct evidence for a cytosolic pool. Supporting Evidence: file:yeast/ACO1/ACO1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion. Cytoplasm. Note=Mainly PMID:15975908 Together, our data indicate that yeast aconitase isoenzymes distribute between two distinct subcellular compartments and participate in two separate metabolic pathways; the glyoxylate shunt in the cytosol and the TCA cycle in mitochondria. |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | ACCEPT | Summary: High-throughput mitochondrial proteome (Reinders et al. 2006) detected Aco1p in purified mitochondria; consistent with its main matrix location. Reason: Consistent with established localisation. Supporting Evidence: file:yeast/ACO1/ACO1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion. Cytoplasm. Note=Mainly |
| GO:0005739 mitochondrion | HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph... | ACCEPT | Summary: Quantitative mitochondrial proteome (Renvoise et al. 2014) detected Aco1p in mitochondria under fermentative and respiratory growth. Reason: Consistent with established localisation. Supporting Evidence: file:yeast/ACO1/ACO1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion. Cytoplasm. Note=Mainly |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA is_active_in mitochondrion for the mitochondrial aconitase clade; correct for ACO1. Reason: Correct inherited location. Supporting Evidence: file:yeast/ACO1/ACO1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion. Cytoplasm. Note=Mainly |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location keyword mapping to mitochondrion; correct. Reason: Correct location. Supporting Evidence: file:yeast/ACO1/ACO1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion. Cytoplasm. Note=Mainly |
| GO:0005758 mitochondrial intermembrane space | TAS Reactome:R-SCE-1252255 | REMOVE | Summary: Reactome TAS derived from the TOM40:TOM70 import reaction (R-SCE-1252255, computationally projected to yeast), in which Aco1p is cargo translocated across the outer membrane. Mature aconitase resides in the matrix (and a small cytosolic pool); there is no evidence it resides in the intermembrane space. Reason: Artifact of modelling a transit step of protein import; not a resident location. Supporting Evidence: file:yeast/ACO1/ACO1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion. Cytoplasm. Note=Mainly |
| GO:0005759 mitochondrial matrix | IDA PMID:15692048 Aconitase couples metabolic regulation to mitochondrial DNA ... | ACCEPT | Summary: Chen et al. identified Aco1p among mtDNA-associated proteins in mitochondria (matrix nucleoids); the TCA-cycle aconitase is a matrix enzyme. Reason: Correct matrix location; directly observed. Supporting Evidence: PMID:15692048 We show that this Krebs-cycle enzyme is essential for mtDNA maintenance independent of its catalytic activity. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA is_active_in cytosol (PTN001705783). For ACO1 a cytosolic pool active in the glyoxylate shunt has been demonstrated, so the inherited location is supported here. Reason: Supported by target-specific evidence (PMID:15975908). Supporting Evidence: PMID:15975908 Together, our data indicate that yeast aconitase isoenzymes distribute between two distinct subcellular compartments and participate in two separate metabolic pathways; the glyoxylate shunt in the cytosol and the TCA cycle in mitochondria. |
| GO:0005829 cytosol | IDA PMID:15975908 Yeast aconitase in two locations and two metabolic pathways:... | ACCEPT | Summary: Regev-Rudzki et al. detected a small cytosolic aconitase pool by alpha-complementation and showed its loss causes a glyoxylate-shunt defect. Reason: Direct experimental evidence for a functional cytosolic pool. Supporting Evidence: PMID:15975908 Together, our data indicate that yeast aconitase isoenzymes distribute between two distinct subcellular compartments and participate in two separate metabolic pathways; the glyoxylate shunt in the cytosol and the TCA cycle in mitochondria. PMID:15975908 Loss of cytosolic aconitase was found to result in a glyoxylate shunt defect |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA placing aconitase activity in the cytosol for the glyoxylate cycle; matches the experimentally shown cytosolic Aco1p. Reason: Consistent with experimental data. Supporting Evidence: PMID:15975908 Together, our data indicate that yeast aconitase isoenzymes distribute between two distinct subcellular compartments and participate in two separate metabolic pathways; the glyoxylate shunt in the cytosol and the TCA cycle in mitochondria. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | KEEP AS NON CORE | Summary: YeastPathways RCA cytosol from the TCA/glyoxylate superpathway (PWY3O-94); holds only for the glyoxylate-shunt portion, already captured by direct evidence. Reason: Redundant with stronger IDA; superpathway-inherited. Supporting Evidence: PMID:15975908 Together, our data indicate that yeast aconitase isoenzymes distribute between two distinct subcellular compartments and participate in two separate metabolic pathways; the glyoxylate shunt in the cytosol and the TCA cycle in mitochondria. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | MARK AS OVER ANNOTATED | Summary: YeastPathways RCA cytosol inherited from the TCA cycle pathway (TCA-EUK-PWY). The TCA-cycle reaction of Aco1p occurs in the mitochondrial matrix, not the cytosol; the cytosolic pool serves the glyoxylate shunt. Reason: Compartment wrongly attached to the TCA-cycle context; cytosol is correct only via the glyoxylate shunt (captured by other rows). Supporting Evidence: PMID:15975908 Together, our data indicate that yeast aconitase isoenzymes distribute between two distinct subcellular compartments and participate in two separate metabolic pathways; the glyoxylate shunt in the cytosol and the TCA cycle in mitochondria. |
| GO:0005829 cytosol | TAS Reactome:R-SCE-1252255 | MARK AS OVER ANNOTATED | Summary: Reactome TAS cytosol from the TOM40:TOM70 import reaction where Aco1p is the cargo in transit. Although Aco1p has a genuine small cytosolic pool, this annotation is based on the pre-import precursor, not that pool. Reason: Basis is an import-transit step; genuine cytosolic location is captured by the IDA. Supporting Evidence: PMID:15975908 Together, our data indicate that yeast aconitase isoenzymes distribute between two distinct subcellular compartments and participate in two separate metabolic pathways; the glyoxylate shunt in the cytosol and the TCA cycle in mitochondria. |
| GO:0006097 glyoxylate cycle | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA involved_in glyoxylate cycle. Supported experimentally: strains in which Aco1p was restricted to mitochondria showed a glyoxylate-shunt growth defect on ethanol-acetate/oleate. Reason: Correct process; cytosolic Aco1p supplies the shunt. Supporting Evidence: PMID:15975908 Together, our data indicate that yeast aconitase isoenzymes distribute between two distinct subcellular compartments and participate in two separate metabolic pathways; the glyoxylate shunt in the cytosol and the TCA cycle in mitochondria. PMID:15975908 Loss of cytosolic aconitase was found to result in a glyoxylate shunt defect |
| GO:0006099 tricarboxylic acid cycle | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA on the PTN000186533 mitochondrial-type aconitase node for tricarboxylic acid cycle; ACO1 is the main TCA aconitase. Reason: Core process. Supporting Evidence: file:yeast/ACO1/ACO1-uniprot.txt Catalyzes the isomerization of citrate to isocitrate via cis- |
| GO:0006099 tricarboxylic acid cycle | IDA PMID:1972545 Molecular cloning of the yeast mitochondrial aconitase gene ... | ACCEPT | Summary: Gangloff et al.: ACO1 encodes mitochondrial aconitase; its loss causes glutamate auxotrophy and inability to use non-fermentable carbon, the classic TCA-cycle defect. Reason: Core process with experimental support. Supporting Evidence: PMID:1972545 Disruption of the gene by deletion-insertion led to glutamate auxotrophy. PMID:23106124 These results indicated that Aco1p mainly serves for the citric acid cycle with minor contribution to lysine biosynthesis, whereas Aco2p does not contribute to the citric acid cycle but is specifically involved in the Ξ±-aminoadipate pathway. |
| GO:0006099 tricarboxylic acid cycle | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (ARBA, InterPro IPR006248, UniPathway UPA00223) for TCA cycle; correct. Reason: Core process. Supporting Evidence: file:yeast/ACO1/ACO1-uniprot.txt Catalyzes the isomerization of citrate to isocitrate via cis- |
| GO:0009060 aerobic respiration | RCA GO_REF:0000123 | KEEP AS NON CORE | Summary: YeastPathways RCA involved_in aerobic respiration from TCA-EUK-PWY. TCA cycle is part of aerobic respiration, so not wrong, but much less specific than the TCA-cycle annotations. Reason: Correct but general parent of the core process. Supporting Evidence: file:yeast/ACO1/ACO1-uniprot.txt Catalyzes the isomerization of citrate to isocitrate via cis- |
| GO:0042645 mitochondrial nucleoid | IDA PMID:10869431 In organello formaldehyde crosslinking of proteins to mtDNA:... | KEEP AS NON CORE | Summary: Kaufman et al. in organello formaldehyde crosslinking identified mtDNA-associated (nucleoid) proteins; Aco1p was among them (later confirmed by PMID:15692048). Reason: Real nucleoid association supporting the mtDNA-maintenance moonlighting role; non-core. Supporting Evidence: PMID:15692048 We show that this Krebs-cycle enzyme is essential for mtDNA maintenance independent of its catalytic activity. |
| GO:0051536 iron-sulfur cluster binding | IDA PMID:31040179 Mitochondria export iron-sulfur and sulfur intermediates to ... | ACCEPT | Summary: Pain lab study of mitochondrial export of Fe-S intermediates (abstract-only cache); curator IDA for iron-sulfur cluster binding presumably reflects Fe-35S labelling of aconitase. Consistent with the known [4Fe-4S] cofactor of Aco1p. Reason: Deferring to curator; consistent with well-established cofactor. Supporting Evidence: file:yeast/ACO1/ACO1-uniprot.txt Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; |
| GO:0051539 4 iron, 4 sulfur cluster binding | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA on the PTN000186533 mitochondrial-type aconitase node for 4 iron, 4 sulfur cluster binding; aconitases require a [4Fe-4S] cluster for catalysis. Reason: Correct cofactor binding. Supporting Evidence: file:yeast/ACO1/ACO1-uniprot.txt Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; |
| GO:0051539 4 iron, 4 sulfur cluster binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO (IPR006248) mapping to 4Fe-4S cluster binding; correct. Reason: Correct cofactor binding. Supporting Evidence: file:yeast/ACO1/ACO1-uniprot.txt Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; |
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Aconitase; required for the tricarboxylic acid (TCA) cycle and also independently required for mitochondrial genome maintenance; component of the mitochondrial nucleoid; mutation leads to glutamate auxotrophy; mutation in human homolog ACO2 is associated with dominant optic nerve atrophy; human homolog ACO2 can complement yeast null mutant
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