Gut2p is the FAD-dependent mitochondrial glycerol-3-phosphate dehydrogenase (EC 1.1.5.3) of S. cerevisiae. Bound to the outer surface of the inner mitochondrial membrane with its active site in the intermembrane space, it oxidises sn-glycerol 3-phosphate to DHAP and passes the electrons via FAD to ubiquinone and the respiratory chain. It has two roles: it is the second step of glycerol utilisation after glycerol kinase Gut1p (gut2 mutants cannot grow on glycerol), and together with cytosolic Gpd1p/Gpd2p it forms the glycerol-3-phosphate shuttle that oxidises cytosolic NADH in respiring cells, alongside the external NADH dehydrogenases Nde1p/Nde2p. Gut2p associates with these dehydrogenases in a supramolecular complex, and active Nde1/2p kinetically inhibits Gut2p. GUT2 transcription is repressed by glucose and derepressed on glycerol, lactate and ethanol; derepression requires the Snf1 kinase, the Hap2/3/4/5 complex acting at a promoter UAS, and, on glycerol, the respiration factor Rsf1.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004368 glycerol-3-phosphate dehydrogenase (quinone) activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000240932 (FAD-dependent mitochondrial GPDH clade; human GPD2, Arabidopsis SDP6, yeast Gut2). Correct core activity. Supporting Evidence: PMID:8256521 A gut2 mutant of Saccharomyces cerevisiae is deficient in the mitochondrial glycerol 3-phosphate dehydrogenase and hence cannot utilize glycerol. file:yeast/GUT2/GUT2-uniprot.txt Reaction=a quinone + sn-glycerol 3-phosphate = dihydroxyacetone |
| GO:0004368 glycerol-3-phosphate dehydrogenase (quinone) activity | IDA PMID:12032156 Kinetic regulation of the mitochondrial glycerol-3-phosphate... | ACCEPT | Summary: IDA (Pahlman 2002): Gut2p-dependent glycerol-3-phosphate oxidation measured in isolated mitochondria, passing electrons to the respiratory chain (ubiquinone). Supporting Evidence: PMID:12032156 glycerol 3-phosphate gives two electrons to the respiratory chain via mitochondrial glycerol-3-phosphate dehydrogenase (Gut2p)-regenerating dihydroxyacetone phosphate PMID:12032156 the activation of NADH dehydrogenase inhibited the Gut2p in such a manner that, at a saturating concentration of NADH, glycerol 3-phosphate is not used as respiratory substrate. |
| GO:0004368 glycerol-3-phosphate dehydrogenase (quinone) activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (ARBA/IPR000447/RHEA:18977/EC 1.1.5.3). Correct. Supporting Evidence: file:yeast/GUT2/GUT2-uniprot.txt Reaction=a quinone + sn-glycerol 3-phosphate = dihydroxyacetone |
| GO:0004368 glycerol-3-phosphate dehydrogenase (quinone) activity | IMP PMID:8256521 GUT2, a gene for mitochondrial glycerol 3-phosphate dehydrog... | ACCEPT | Summary: IMP (Ronnow 1993): gut2 mutants lack mitochondrial G3P dehydrogenase and cannot use glycerol; putative FAD-binding domain. Supporting Evidence: PMID:8256521 A gut2 mutant of Saccharomyces cerevisiae is deficient in the mitochondrial glycerol 3-phosphate dehydrogenase and hence cannot utilize glycerol. PMID:8256521 A putative flavin-binding domain, located at the amino terminus, was identified |
| GO:0004368 glycerol-3-phosphate dehydrogenase (quinone) activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways glycerol degradation (reaction with ubiquinone-6, EC 1.1.5.3). Correct. Supporting Evidence: file:yeast/GUT2/GUT2-uniprot.txt Reaction=a quinone + sn-glycerol 3-phosphate = dihydroxyacetone |
| GO:0005739 mitochondrion | HDA PMID:14576278 The proteome of Saccharomyces cerevisiae mitochondria. | ACCEPT | Summary: HDA, mitochondrial proteome (Sickmann 2003). Correct. Supporting Evidence: PMID:14576278 The proteins of highly pure yeast mitochondria were separated by several independent methods and analyzed by tandem MS. |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | ACCEPT | Summary: HDA, PROMITO mitochondrial proteome (Reinders 2006). Correct. Supporting Evidence: PMID:16823961 A total of 851 different proteins (PROMITO dataset) were identified |
| GO:0005739 mitochondrion | HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph... | ACCEPT | Summary: HDA, quantitative mitochondrial proteome (Renvoise 2014). Correct. Supporting Evidence: PMID:24769239 we performed an overall quantitative proteomic and phosphoproteomic study of isolated mitochondria extracted from yeast grown on fermentative (glucose or galactose) and respiratory (lactate) media |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: IBA is_active_in mitochondrion from PTN000240934. Correct. Supporting Evidence: PMID:12032156 Both Nde1p/Nde2p and Gut2p are located in the inner mitochondrial membrane with catalytic sites facing the intermembranal space. |
| GO:0005739 mitochondrion | IDA PMID:11502169 Yeast mitochondrial dehydrogenases are associated in a supra... | ACCEPT | Summary: IDA (Grandier-Vazeille 2001): Gut2p found in a native mitochondrial supercomplex of IMS-facing dehydrogenases. Supporting Evidence: PMID:11502169 The complex was found to contain the five known intermembrane space-facing dehydrogenases, namely two external NADH-dehydrogenases Nde1p and Nde2p, glycerol-3-phosphate dehydrogenase Gut2p |
| GO:0005739 mitochondrion | IMP PMID:8256521 GUT2, a gene for mitochondrial glycerol 3-phosphate dehydrog... | ACCEPT | Summary: IMP (Ronnow 1993): gut2 mutants lack the mitochondrial G3P dehydrogenase activity. Supporting Evidence: PMID:8256521 A gut2 mutant of Saccharomyces cerevisiae is deficient in the mitochondrial glycerol 3-phosphate dehydrogenase and hence cannot utilize glycerol. |
| GO:0005739 mitochondrion | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways glycerol degradation; mitochondrial compartment. Correct. Supporting Evidence: PMID:12032156 Both Nde1p/Nde2p and Gut2p are located in the inner mitochondrial membrane with catalytic sites facing the intermembranal space. |
| GO:0005741 mitochondrial outer membrane | IDA PMID:16689936 Integral membrane proteins in the mitochondrial outer membra... | MARK AS OVER ANNOTATED | Summary: IDA from a proteomic survey of purified outer membrane (Burri 2006). Targeted work places Gut2p on the inner membrane with its active site in the IMS, and it is imported via the presequence pathway with release to the IMS; an outer-membrane assignment most likely reflects co-purifying IMS/inner-membrane material. Reason: Contradicted by targeted inner-membrane/IMS localization; kept (not removed) as the curator saw the dataset. Supporting Evidence: PMID:16689936 Initial proteomics on the outer membrane from yeast mitochondria suggest that while most of the protein components are integral in the membrane PMID:12032156 Both Nde1p/Nde2p and Gut2p are located in the inner mitochondrial membrane with catalytic sites facing the intermembranal space. PMID:22984289 only three proteins of the IMS (Gut2, Cyb2, and Mcr1) have been shown to take this import route in yeast mitochondria |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt SubCell 'Mitochondrion inner membrane'. Gut2p is attached to the outer face of the inner membrane with catalytic site in the IMS. Supporting Evidence: file:yeast/GUT2/GUT2-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane PMID:12032156 Both Nde1p/Nde2p and Gut2p are located in the inner mitochondrial membrane with catalytic sites facing the intermembranal space. |
| GO:0005758 mitochondrial intermembrane space | EXP PMID:22984289 Intermembrane space proteome of yeast mitochondria. | ACCEPT | Summary: EXP (Vogtle 2012, IMS proteome): Gut2 is an IMS protein imported via the presequence pathway with lateral arrest/release to the IMS. Consistent with its IMS-facing active site. Supporting Evidence: PMID:22984289 only three proteins of the IMS (Gut2, Cyb2, and Mcr1) have been shown to take this import route in yeast mitochondria PMID:12032156 Both Nde1p/Nde2p and Gut2p are located in the inner mitochondrial membrane with catalytic sites facing the intermembranal space. |
| GO:0005758 mitochondrial intermembrane space | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt SubCell 'Mitochondrion intermembrane space'. Correct. Supporting Evidence: file:yeast/GUT2/GUT2-uniprot.txt Mitochondrion intermembrane space |
| GO:0006071 glycerol metabolic process | IMP PMID:8256521 GUT2, a gene for mitochondrial glycerol 3-phosphate dehydrog... | MODIFY | Summary: IMP (Ronnow 1993): gut2 disruption gives a glycerol non-utilising phenotype. The evidence supports the more specific glycerol catabolic process. Proposed replacements: glycerol catabolic process Supporting Evidence: PMID:8256521 Disruption of the ORF leads to a glycerol non-utilizing phenotype. |
| GO:0006072 glycerol-3-phosphate metabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000240932; correct (Gut2p oxidises G3P), general. Supporting Evidence: file:yeast/GUT2/GUT2-uniprot.txt Reaction=a quinone + sn-glycerol 3-phosphate = dihydroxyacetone |
| GO:0006072 glycerol-3-phosphate metabolic process | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO (IPR000447 FAD-dependent G3P DH); correct, general. Supporting Evidence: file:yeast/GUT2/GUT2-uniprot.txt Reaction=a quinone + sn-glycerol 3-phosphate = dihydroxyacetone |
| GO:0006127 glycerol-3-phosphate shuttle | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000240934. Gut2p is the mitochondrial, quinone-reducing half of the glycerol-3-phosphate shuttle with cytosolic Gpd1p/Gpd2p, transferring cytosolic NADH-derived electrons to the respiratory chain; the shuttle is not essential but contributes when external NADH dehydrogenases are absent. Supporting Evidence: PMID:10781551 a glycerol-3-phosphate shuttle consisting of soluble (Gpd1p or Gpd2p) and membrane-bound (Gut2p) glycerol-3-phosphate dehydrogenases PMID:12032156 glycerol 3-phosphate gives two electrons to the respiratory chain via mitochondrial glycerol-3-phosphate dehydrogenase (Gut2p)-regenerating dihydroxyacetone phosphate PMID:10781551 Apparently, the glycerol-3-phosphate shuttle is not essential for respiratory glucose dissimilation. |
| GO:0019563 glycerol catabolic process | IEA GO_REF:0000041 | ACCEPT | Summary: UniPathway mapping (UPA00618 glycerol degradation via glycerol kinase pathway). Correct core process. Supporting Evidence: PMID:8256521 A gut2 mutant of Saccharomyces cerevisiae is deficient in the mitochondrial glycerol 3-phosphate dehydrogenase and hence cannot utilize glycerol. |
| GO:0019563 glycerol catabolic process | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways glycerol degradation. Correct. Supporting Evidence: PMID:8256521 Disruption of the ORF leads to a glycerol non-utilizing phenotype. |
| GO:0031966 mitochondrial membrane | IEA GO_REF:0000117 | TOO GENERAL | Summary: ARBA mitochondrial membrane; correct, less specific than inner membrane. Supporting Evidence: PMID:12032156 Both Nde1p/Nde2p and Gut2p are located in the inner mitochondrial membrane with catalytic sites facing the intermembranal space. |
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Download this section (compressed HTML)Q: How is Gut2p partitioned between glycerol catabolism and the NADH shuttle during growth on glycerol versus respiratory glucose growth, and how strongly does Nde1/2 activity inhibit it in vivo?
Experiment: Measure G3P-driven oxygen consumption in mitochondria from nde1 nde2 and wild-type cells grown on glycerol versus glucose, and resolve Gut2p topology by protease protection after outer-membrane rupture.
Mitochondrial glycerol-3-phosphate dehydrogenase; expression is repressed by both glucose and cAMP and derepressed by non-fermentable carbon sources in a Snf1p, Rsf1p, Hap2/3/4/5 complex dependent manner
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