ARH1 (YDR376W) encodes the essential mitochondrial NADPH-adrenodoxin (ferredoxin) reductase of S. cerevisiae. It is an FAD-containing flavoprotein of the ferredoxin-NADP reductase type 1 family that fractionates with the inner mitochondrial membrane, where it is thought to associate peripherally on the matrix side next to its soluble partner Yah1. Arh1 transfers electrons from NADPH (and less efficiently NADH) to the [2Fe-2S] ferredoxin Yah1, and the reduced ferredoxin then supplies electrons for Fe-S cluster synthesis on the Isu1 scaffold, for the Cox15-dependent conversion of heme O to heme A, and for coenzyme Q6 biosynthesis (probably the Coq6 hydroxylation). Loss of Arh1 impairs Fe-S protein activities and causes cellular and mitochondrial iron dysregulation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004324 ferredoxin-NADP+ reductase activity | IDA PMID:9727014 Characterization of recombinant adrenodoxin reductase homolo... | ACCEPT | Summary: Recombinant Arh1p transfers electrons from NADPH (and NADH) to bovine adrenodoxin, cytochrome c and ferricyanide and supports an in vitro adrenodoxin-dependent P450 11beta-hydroxylase assay. Reason: Core activity; GO:0004324 is the GO term for EC 1.18.1.6 adrenodoxin reductase since NADPH-adrenodoxin reductase activity was obsoleted. Supporting Evidence: PMID:9727014 We demonstrate the capacity of recombinant Arh1p, made in Escherichia coli, to substitute for its mammalian homologue PMID:9727014 Electrons could be transferred from NADPH and NADH as measured in the cytochrome c reduction assay file:yeast/ARH1/ARH1-uniprot.txt Reaction=2 reduced [adrenodoxin] + NADP(+) + H(+) = 2 oxidized |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | ACCEPT | Summary: Arh1 detected in purified mitochondria by proteomics (PMID:16823961). Reason: Root organelle term from whole-organelle proteomics, which cannot resolve the sub-compartment; ACCEPT under the organelle policy. Targeted fractionation (PMID:9727014) gives the inner-membrane location. Supporting Evidence: PMID:9818721 Immunodetection with a specific polyclonal antibody located the gene product in the mitochondrial fraction |
| GO:0005739 mitochondrion | HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph... | ACCEPT | Summary: Arh1 detected in purified mitochondria by proteomics (PMID:24769239). Reason: Root organelle term from whole-organelle proteomics, which cannot resolve the sub-compartment; ACCEPT under the organelle policy. Targeted fractionation (PMID:9727014) gives the inner-membrane location. Supporting Evidence: PMID:9818721 Immunodetection with a specific polyclonal antibody located the gene product in the mitochondrial fraction |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: IBA mitochondrion from the adrenodoxin reductase node (fly, rat, human, yeast members). Reason: PAINT node PTN000234268 (adrenodoxin reductase clade, seeded by fly, rat, human and yeast Arh1 itself) places the mitochondrial location; Arh1 sits inside that clade and has direct immunodetection in the mitochondrial fraction. The organelle claim holds; the inner-membrane rows give the sub-compartment. Supporting Evidence: PMID:9818721 Immunodetection with a specific polyclonal antibody located the gene product in the mitochondrial fraction |
| GO:0005743 mitochondrial inner membrane | EXP PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | ACCEPT | Summary: UniProt cites the PROMITO mitochondrial proteome for inner membrane location. Reason: The proteome paper (abstract only) is one of three UniProt citations for the inner-membrane location; the claim itself is supported by the subcellular fractionation in PMID:9727014, so the row stands. Supporting Evidence: PMID:9727014 Subcellular fractionation studies have localized Arh1p to the inner membrane of yeast mitochondria |
| GO:0005743 mitochondrial inner membrane | EXP PMID:9818721 ARH1 of Saccharomyces cerevisiae: a new essential gene that ... | ACCEPT | Summary: Manzella et al. detected Arh1 in the mitochondrial fraction; UniProt records inner membrane. Reason: Consistent with fractionation data. Supporting Evidence: PMID:9818721 Immunodetection with a specific polyclonal antibody located the gene product in the mitochondrial fraction PMID:9727014 Subcellular fractionation studies have localized Arh1p to the inner membrane of yeast mitochondria |
| GO:0005743 mitochondrial inner membrane | IDA PMID:9727014 Characterization of recombinant adrenodoxin reductase homolo... | ACCEPT | Summary: Subcellular fractionation localized Arh1p to the mitochondrial inner membrane. Reason: Direct fractionation evidence. UniProt's peripheral-membrane qualifier is a curator inference (ECO:0000305), so no extrinsic-component sub-term is added. Supporting Evidence: PMID:9727014 Subcellular fractionation studies have localized Arh1p to the inner membrane of yeast mitochondria |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location mapping (SL-0168). Reason: The SubCell mapping agrees with the experimental rows for the same term. Supporting Evidence: PMID:9727014 Subcellular fractionation studies have localized Arh1p to the inner membrane of yeast mitochondria |
| GO:0006744 ubiquinone biosynthetic process | IMP PMID:20534343 Involvement of mitochondrial ferredoxin and para-aminobenzoi... | ACCEPT | Summary: Gal-ARH1 depletion blocks Q6 biosynthesis with accumulation of 3-hexaprenyl-4-hydroxyphenol/-aminophenol; Arh1 reduces Yah1, which supplies electrons for the Coq6 hydroxylation. Reason: Arh1 performs the NADPH-oxidizing step of the electron chain that a CoQ hydroxylation consumes; involvement is direct but shared with other pathways. Supporting Evidence: PMID:20534343 the mitochondrial ferredoxin Yah1p and the ferredoxin reductase Arh1p are required for Q(6) biosynthesis |
| GO:0006879 intracellular iron ion homeostasis | IMP PMID:11035018 Adrenodoxin reductase homolog (Arh1p) of yeast mitochondria ... | KEEP AS NON CORE | Summary: Arh1 depletion dysregulates cellular iron uptake and causes mitochondrial iron overload, together with loss of Fe-S enzyme activities. Reason: Iron dysregulation is a downstream consequence of defective Fe-S cluster assembly (iron regulon signalling depends on mitochondrial Fe-S cluster synthesis); Arh1 is not itself an iron homeostasis regulator. The term is kept as the observed phenotype-level involvement but is peripheral. Supporting Evidence: PMID:11035018 Thus, Arh1p is required for control of cellular and mitochondrial iron levels and for the activities of Fe-S cluster proteins |
| GO:0016491 oxidoreductase activity | IBA GO_REF:0000033 | TOO GENERAL | Summary: IBA oxidoreductase activity from the adrenodoxin reductase family node; true but general. Reason: PTN000234102 is a deep, broad node (plant, fungal, bacterial and animal reductases) and its oxidoreductase assertion is correct for Arh1, but it is entailed by the specific ferredoxin-NADP+ reductase activity (GO:0004324) accepted on the IDA row; the human FDXR review treats its oxidoreductase row the same way. Supporting Evidence: PMID:9727014 Electrons could be transferred from NADPH and NADH as measured in the cytochrome c reduction assay |
| GO:0016491 oxidoreductase activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO oxidoreductase activity (IPR021163/IPR055275); true but general. Reason: True of the protein but entailed by the accepted GO:0004324 ferredoxin-NADP+ reductase activity; consistent with the IBA row for the same term. Supporting Evidence: PMID:9727014 Electrons could be transferred from NADPH and NADH as measured in the cytochrome c reduction assay |
| GO:0016226 iron-sulfur cluster assembly | IMP PMID:11035018 Adrenodoxin reductase homolog (Arh1p) of yeast mitochondria ... | NEW | Summary: Arh1 depletion abolishes aconitase and other mitochondrial and cytosolic Fe-S protein activities without lowering protein levels, and the Arh1-Yah1 chain is established as the electron source for Fe-S cluster synthesis on Isu1 (PMID:12970193). Its partner ferredoxin YAH1 already carries GO:0016226 in GOA, but ARH1 does not. Reason: Arh1 contributes the cofactor activity a step depends on: it reduces Yah1 with NADPH, and the reduced Yah1 supplies the electrons consumed during cluster formation on Isu1. This is the same electron-supply role for which GOA already annotates Arh1 to ubiquinone biosynthesis. Comparator check: the S. pombe ortholog arh1 (O59710) carries [2Fe-2S] cluster assembly (GO:0044571, IC, PomBase) and the partner ferredoxin Yah1 carries GO:0016226; human FDXR does not, so the convention is mixed rather than a systematic exclusion of reductases. The general parent term is used because Yah1 feeds both [2Fe-2S] and [4Fe-4S] cluster formation. Supporting Evidence: PMID:11035018 Thus, Arh1p is required for control of cellular and mitochondrial iron levels and for the activities of Fe-S cluster proteins PMID:12970193 the requirement of an electron transfer chain consisting of ferredoxin (yeast Yah1p) and ferredoxin reductase (yeast Arh1p) is well established |
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Oxidoreductase of the mitochondrial inner membrane; involved in cytoplasmic and mitochondrial iron homeostasis and required for activity of Fe-S cluster-containing enzymes; one of the few mitochondrial proteins essential for viability
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