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-Structure paper
| Title | Global conformations of complex I are distinguished by the binding of a unique interdomain bridging subunit. |
|---|---|
| Journal, issue, pages | Sci Adv, Vol. 11, Issue 40, Page eadz0693, Year 2025 |
| Publish date | Oct 3, 2025 |
Authors | Chris Seunggyu Lee / Daniel N Grba / John J Wright / Bozhidar S Ivanov / Judy Hirst / ![]() |
| PubMed Abstract | Complex I (CI; NADH ubiquinone oxidoreductase) is central to energy generation and metabolic homeostasis in mammalian cells but contributes to adverse outcome pathways under challenging conditions. ...Complex I (CI; NADH ubiquinone oxidoreductase) is central to energy generation and metabolic homeostasis in mammalian cells but contributes to adverse outcome pathways under challenging conditions. During ischemia, mammalian CI transitions from a turnover-ready, structurally "closed" state toward a dormant "open" state that prevents it from functioning in reverse during reperfusion to produce reactive oxygen species. Unfortunately, simpler, genetically tractable CI models do not recapitulate the same regulatory behavior, compromising mechanistic studies. Here, we report the structure of isolated CI from the yeast (-CI) and identify distinct closed and open states that resemble those of mammalian CI. Notably, a hitherto-unknown protein (NUQM) completes an interdomain bridge in only the closed state, implying that NUQM stabilizes it by restricting the conformational changes of opening. The direct correlation of NUQM binding with closed/open status in -CI provides opportunities for investigating regulatory mechanisms relevant to reversible catalysis and ischemia-reperfusion injury. |
External links | Sci Adv / PubMed:41032597 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.8 - 20.0 Å |
| Structure data | EMDB-52875, PDB-9iho: EMDB-52876, PDB-9ihp: EMDB-52877, PDB-9ihq: EMDB-52878, PDB-9ihr: ![]() EMDB-52890: NUQM-free state of Pichia pastoris mitochondrial complex I reconstituted into proteoliposomes ![]() EMDB-52891: NUQM-bound state of Pichia pastoris mitochondrial complex I reconstituted into proteoliposomes ![]() EMDB-52892: Flavoprotein (NUHM and NUBM)-free state of Pichia pastoris mitochondrial complex I reconstituted into proteoliposomes ![]() EMDB-52893: Flavoprotein (NUHM and NUBM)-containing state of Pichia pastoris mitochondrial complex I reconstituted into proteoliposomes |
| Chemicals | ![]() ChemComp-SF4: ![]() ChemComp-PLC: ![]() ChemComp-K: ![]() ChemComp-3PE: ![]() ChemComp-CDL: ![]() ChemComp-NDP: ![]() ChemComp-ZN: ![]() ChemComp-EHZ: ![]() ChemComp-FES: ![]() ChemComp-FMN: |
| Source |
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Keywords | MEMBRANE PROTEIN / NADH:ubiquinone oxidoreductase nanodisc membrane protein complex |
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komagataella pastoris (fungus)
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