NDE2 encodes the minor external type-II NADH:ubiquinone oxidoreductase (NDH-2, EC 1.6.5.9) of S. cerevisiae mitochondria, a paralog of NDE1 from the whole-genome duplication. Like Nde1p it is a single-subunit flavoprotein on the intermembrane-space face of the inner membrane that oxidises cytosolic NADH and reduces ubiquinone without proton pumping. Its contribution is detectable only genetically: an nde2 single mutant has normal mitochondrial NADH oxidation, but NADH-dependent respiration is completely abolished in the nde1 nde2 double mutant, which grows more slowly on ethanol and galactose. Nde2p co-purifies with Nde1p, Ndi1p and other intermembrane-space-facing dehydrogenases in a supramolecular assembly. Active external NADH dehydrogenase (Nde1/Nde2) kinetically inhibits the glycerol-3-phosphate dehydrogenase Gut2, the other route for cytosolic NADH oxidation, so that glycerol 3-phosphate is not used at saturating NADH.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003954 NADH dehydrogenase activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO (NDH-2 family) mapping to NADH dehydrogenase activity. Correct for Nde2p by family membership and genetic data. Supporting Evidence: PMID:9733747 NADH-dependent mitochondrial respiration was completely abolished in an nde1Delta nde2Delta double mutant. |
| GO:0003954 NADH dehydrogenase activity | ISS PMID:9696750 Identification of a cytosolically directed NADH dehydrogenas... | ACCEPT | Summary: ISS based on similarity to NDI1/NDE1 described in Small & McAlister-Henn. In that study disruption of NDE2 (NDH2) alone had no effect on mitochondrial NADH dehydrogenase activity, so the inference rests on sequence similarity; it is nonetheless supported by the later double-mutant data. Supporting Evidence: PMID:9696750 A search of the S. cerevisiae genome sequence database revealed two ORFs, YMR145c and YDL085w , with extensive sequence similarity to the previously identified gene ( NDI1 , ORF YML120C ) encoding the internal form of mitochondrial NADH dehydrogenase PMID:9696750 Disruption of a closely related gene designated NDH2 has no effect on these properties. PMID:9733747 NADH-dependent mitochondrial respiration was completely abolished in an nde1Delta nde2Delta double mutant. |
| GO:0003954 NADH dehydrogenase activity | ISS PMID:9733747 The Saccharomyces cerevisiae NDE1 and NDE2 genes encode sepa... | ACCEPT | Summary: ISS citing Luttik et al., where the nde2 single mutant had no effect but the nde1 nde2 double mutant completely lost NADH-dependent respiration, indicating Nde2p provides residual external NADH dehydrogenase activity. Supporting Evidence: PMID:9733747 Compared with the wild type, rates of mitochondrial NADH oxidation were about 3-fold reduced in an nde1Delta mutant and unaffected in an nde2Delta mutant. PMID:9733747 NADH-dependent mitochondrial respiration was completely abolished in an nde1Delta nde2Delta double mutant. |
| GO:0005739 mitochondrion | HDA PMID:14576278 The proteome of Saccharomyces cerevisiae mitochondria. | ACCEPT | Summary: Mitochondrial proteome (Sickmann et al.) detected Nde2p; source of UniProt's IMS assignment. Supporting Evidence: file:yeast/NDE2/NDE2-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion intermembrane space |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | ACCEPT | Summary: Mitochondrial proteome survey detected Nde2p. Supporting Evidence: file:yeast/NDE2/NDE2-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion intermembrane space |
| GO:0005739 mitochondrion | HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph... | ACCEPT | Summary: Quantitative mitochondrial proteomics detected Nde2p. Consistent with its expected location. Supporting Evidence: file:yeast/NDE2/NDE2-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion intermembrane space |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for mitochondrial localisation of the NDH-2 family. Correct; Nde2p is detected in mitochondria and contributes to external NADH oxidation. Supporting Evidence: PMID:11502169 two external NADH-dehydrogenases Nde1p and Nde2p file:yeast/NDE2/NDE2-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion intermembrane space |
| GO:0005739 mitochondrion | IDA PMID:11502169 Yeast mitochondrial dehydrogenases are associated in a supra... | ACCEPT | Summary: Nde2p was identified by Edman/MS in a native mitochondrial supramolecular complex of intermembrane-space-facing dehydrogenases. Supporting Evidence: PMID:11502169 two external NADH-dehydrogenases Nde1p and Nde2p |
| GO:0005739 mitochondrion | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA prediction of mitochondrion; correct and consistent with proteomic and genetic data. Supporting Evidence: file:yeast/NDE2/NDE2-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion intermembrane space |
| GO:0005739 mitochondrion | IMP PMID:9733747 The Saccharomyces cerevisiae NDE1 and NDE2 genes encode sepa... | ACCEPT | Summary: Loss of residual NADH-dependent respiration in mitochondria of the nde1 nde2 double mutant (relative to nde1) attributes this mitochondrial activity to Nde2p. Supporting Evidence: PMID:9733747 NADH-dependent mitochondrial respiration was completely abolished in an nde1Delta nde2Delta double mutant. |
| GO:0005758 mitochondrial intermembrane space | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping to mitochondrial intermembrane space (from mitochondrial proteomics). Consistent with an external NADH dehydrogenase whose active site faces the IMS. Supporting Evidence: file:yeast/NDE2/NDE2-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion intermembrane space PMID:9733747 S. cerevisiae exhibits another mitochondrial NADH-dehydrogenase activity, which oxidizes NADH at the cytosolic side of the inner membrane. |
| GO:0015980 energy derivation by oxidation of organic compounds | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA prediction of the broad term 'energy derivation by oxidation of organic compounds'. Not wrong, but very general. Reason: Broad ancestor; the specific process is mitochondrial electron transport from NADH to ubiquinone. Supporting Evidence: PMID:9733747 NADH-dependent mitochondrial respiration was completely abolished in an nde1Delta nde2Delta double mutant. |
| GO:0016491 oxidoreductase activity | IBA GO_REF:0000033 | MODIFY | Summary: PAINT IBA giving the generic parent 'oxidoreductase activity' to the NDH-2 family. Correct but uninformative for Nde2p. Reason: Replace with the specific non-electrogenic NADH:ubiquinone oxidoreductase term inferred for NDH-2 family members. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: GO_REF:0000033 · PAINT NDH-2 family node SUPPORTS TRANSFER Transfer of the generic oxidoreductase parent is valid; only the granularity is inadequate. Proposed replacements: NADH dehydrogenase (ubiquinone) (non-electrogenic) activity Supporting Evidence: PMID:9733747 NADH-dependent mitochondrial respiration was completely abolished in an nde1Delta nde2Delta double mutant. file:yeast/NDE2/NDE2-uniprot.txt Reaction=a ubiquinone + NADH + H(+) = a ubiquinol + NAD(+); |
| GO:0016491 oxidoreductase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO mapping to generic 'oxidoreductase activity'. Correct but uninformative. Reason: Replace with the specific NDH-2 activity term. Proposed replacements: NADH dehydrogenase (ubiquinone) (non-electrogenic) activity Supporting Evidence: file:yeast/NDE2/NDE2-uniprot.txt Reaction=a ubiquinone + NADH + H(+) = a ubiquinol + NAD(+); |
| GO:0019655 pyruvate fermentation to ethanol | IMP PMID:9733747 The Saccharomyces cerevisiae NDE1 and NDE2 genes encode sepa... | MARK AS OVER ANNOTATED | Summary: Luttik et al. show NDE1/NDE2 provide respiratory oxidation of cytosolic NADH; in glucose-limited chemostats the double mutant was still essentially respiratory. Nde2p does not perform any step of pyruvate-to-ethanol conversion; any shift of NADH reoxidation towards fermentation in mutants is an indirect effect. Reason: Indirect metabolic consequence, not participation in pyruvate fermentation to ethanol. Supporting Evidence: PMID:9733747 Glucose metabolism in aerobic, glucose-limited chemostat cultures (D = 0.10 h-1) of an nde1Delta nde2Delta mutant was essentially respiratory. |
| GO:0050136 NADH dehydrogenase (quinone) (non-electrogenic) activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (EC 1.6.5.9) for non-electrogenic NADH:quinone oxidoreductase activity. Consistent with Nde2p being an NDH-2 whose loss (with NDE1) abolishes NADH-dependent respiration. Supporting Evidence: PMID:9733747 NADH-dependent mitochondrial respiration was completely abolished in an nde1Delta nde2Delta double mutant. file:yeast/NDE2/NDE2-uniprot.txt Reaction=a ubiquinone + NADH + H(+) = a ubiquinol + NAD(+); |
| GO:0120555 NADH dehydrogenase (ubiquinone) (non-electrogenic) activity | IEA GO_REF:0000116 | ACCEPT | Summary: Rhea-based IEA for ubiquinone-specific NDH-2 activity. Consistent with family membership and the double-mutant phenotype; no purified-enzyme data exist for Nde2p. Supporting Evidence: file:yeast/NDE2/NDE2-uniprot.txt Reaction=a ubiquinone + NADH + H(+) = a ubiquinol + NAD(+); PMID:9733747 NADH-dependent mitochondrial respiration was completely abolished in an nde1Delta nde2Delta double mutant. |
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Download this section (compressed HTML)Q: Under which growth conditions (if any) does Nde2p make a quantitatively significant contribution to cytosolic NADH oxidation, given that the nde2 single mutant has no detectable phenotype?
Experiment: Measure NADH-dependent respiration and Nde2p abundance in nde1 mutants across carbon sources and growth phases to define when the minor paralog is expressed and active.
Mitochondrial external NADH dehydrogenase; catalyzes the oxidation of cytosolic NADH; Nde1p and Nde2p are involved in providing the cytosolic NADH to the mitochondrial respiratory chain; NDE2 has a paralog, NDE1, that arose from the whole genome duplication
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