Sqor encodes the Drosophila melanogaster sulfide:quinone oxidoreductase, an FAD-dependent flavoprotein of the SQRD family orthologous to human SQOR. By orthology it catalyses the first and committed step of mitochondrial hydrogen sulfide oxidation: it oxidizes H2S, transferring the sulfane sulfur to an acceptor (glutathione, giving S-sulfanylglutathione, or sulfite, giving thiosulfate) and the electrons via FAD to ubiquinone, feeding the respiratory chain. It is expected to act at the matrix face of the inner mitochondrial membrane. The fly enzyme has not been characterized; Sqor transcript levels are altered in sulfite oxidase (shop) mutant larvae in a dietary cysteine-dependent manner.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | MODIFY | Summary: Mitochondrion by phylogenetic inference (PTN000066987; donors fission yeast hmt2, human SQOR). Reason: Correct but general. SQOR reduces ubiquinone and is a monotopic protein of the inner mitochondrial membrane; the reaction requires access to the membrane quinone pool (UniProt reactions use ubiquinone-10), so mitochondrial inner membrane is the specific location. Applied to both mitochondrion rows. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Proposed replacements: mitochondrial inner membrane Supporting Evidence: file:DROME/Sqor/Sqor-uniprot.txt ubiquinone-10 + hydrogen sulfide + glutathione + H(+) |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | MODIFY | Summary: Mitochondrion from ARBA/UniProt subcellular location. Reason: Correct but general; replace with mitochondrial inner membrane as for the IBA row. Proposed replacements: mitochondrial inner membrane |
| GO:0016491 oxidoreductase activity | IEA GO_REF:0000002 | MODIFY | Summary: Oxidoreductase activity from InterPro. Reason: Uninformative parent; replace with GO:0106436, already annotated. Proposed replacements: glutathione-dependent sulfide quinone oxidoreductase activity |
| GO:0019418 sulfide oxidation | ISS GO_REF:0000024 | ACCEPT | Summary: Sulfide oxidation transferred from human SQOR (Q9Y6N5). Reason: SQOR performs the first step of mitochondrial sulfide oxidation; core process by orthology. |
| GO:0070224 sulfide:quinone oxidoreductase activity | IBA GO_REF:0000033 | MODIFY | Summary: Sulfide:quinone oxidoreductase activity (sulfane sulfur product) by phylogenetic inference (PTN000066985). Reason: GO:0070224 describes the bacterial-type reaction releasing elemental sulfane sulfur. The animal enzyme transfers the sulfane sulfur to glutathione (or sulfite), and UniProt assigns the glutathione-dependent reaction (RHEA:55156) to fly Sqor; the matching term GO:0106436 is already annotated (IEA, ISS). The two GO terms are siblings, so this is a refinement to the reaction the animal enzyme performs. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Proposed replacements: glutathione-dependent sulfide quinone oxidoreductase activity Supporting Evidence: file:DROME/Sqor/Sqor-uniprot.txt Xref=Rhea:RHEA:55156 |
| GO:0070224 sulfide:quinone oxidoreductase activity | IEA GO_REF:0000117 | MODIFY | Summary: Sulfide:quinone oxidoreductase activity from ARBA. Reason: As for the IBA row; replace with the glutathione-dependent activity GO:0106436. Proposed replacements: glutathione-dependent sulfide quinone oxidoreductase activity |
| GO:0071949 FAD binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: FAD binding by phylogenetic inference (PTN000066985). Reason: SQOR is a flavoprotein with a bound FAD that relays electrons to ubiquinone; correct and specific cofactor term, non-core. Propagation Review Root cause: NO FAILURE NON CORE |
| GO:0106436 glutathione-dependent sulfide quinone oxidoreductase activity | IEA GO_REF:0000003 | ACCEPT | Summary: Glutathione-dependent SQOR activity from EC 1.8.5.8. Reason: Specific core activity for the animal SQOR family. Support is family classification of fly Sqor in the mitochondrial (animal) SQOR subfamily; the glutathione-dependent reaction is experimentally established for the human ortholog, not for the fly protein, and the UniProt catalytic-activity lines for this entry are ARBA predictions and are not cited. Supporting Evidence: file:DROME/Sqor/Sqor-uniprot.txt PANTHER; PTHR10632:SF2; SULFIDE:QUINONE OXIDOREDUCTASE, MITOCHONDRIAL; 1. file:DROME/Sqor/Sqor-uniprot.txt InterPro; IPR015904; Sulphide_quinone_reductase. |
| GO:0106436 glutathione-dependent sulfide quinone oxidoreductase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Glutathione-dependent SQOR activity transferred from human SQOR (Q9Y6N5). Reason: Core activity by orthology; untested in flies. Support is family classification of fly Sqor in the mitochondrial (animal) SQOR subfamily, which contains the human donor SQOR. Supporting Evidence: file:DROME/Sqor/Sqor-uniprot.txt PANTHER; PTHR10632:SF2; SULFIDE:QUINONE OXIDOREDUCTASE, MITOCHONDRIAL; 1. file:DROME/Sqor/Sqor-uniprot.txt InterPro; IPR015904; Sulphide_quinone_reductase. |
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Download this section (compressed HTML)Q: Is Sqor required for sulfide detoxification in flies, and does it contribute to H2S-dependent effects on lifespan under dietary restriction?
Experiment: Measure H2S oxidation by isolated mitochondria from Sqor mutant and control flies, and sulfide tolerance of the mutants.
Hypothesis: Sqor is the main entry point for mitochondrial sulfide oxidation in flies.
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