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-Structure paper
タイトル | Structural insights into respiratory complex I deficiency and assembly from the mitochondrial disease-related ndufs4 mouse. |
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ジャーナル・号・ページ | EMBO J, Vol. 43, Issue 2, Page 225-249, Year 2024 |
掲載日 | 2024年1月2日 |
著者 | Zhan Yin / Ahmed-Noor A Agip / Hannah R Bridges / Judy Hirst / |
PubMed 要旨 | Respiratory complex I (NADH:ubiquinone oxidoreductase) is essential for cellular energy production and NAD homeostasis. Complex I mutations cause neuromuscular, mitochondrial diseases, such as Leigh ...Respiratory complex I (NADH:ubiquinone oxidoreductase) is essential for cellular energy production and NAD homeostasis. Complex I mutations cause neuromuscular, mitochondrial diseases, such as Leigh Syndrome, but their molecular-level consequences remain poorly understood. Here, we use a popular complex I-linked mitochondrial disease model, the ndufs4 mouse, to define the structural, biochemical, and functional consequences of the absence of subunit NDUFS4. Cryo-EM analyses of the complex I from ndufs4 mouse hearts revealed a loose association of the NADH-dehydrogenase module, and discrete classes containing either assembly factor NDUFAF2 or subunit NDUFS6. Subunit NDUFA12, which replaces its paralogue NDUFAF2 in mature complex I, is absent from all classes, compounding the deletion of NDUFS4 and preventing maturation of an NDUFS4-free enzyme. We propose that NDUFAF2 recruits the NADH-dehydrogenase module during assembly of the complex. Taken together, the findings provide new molecular-level understanding of the ndufs4 mouse model and complex I-linked mitochondrial disease. |
リンク | EMBO J / PubMed:38177503 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.2 - 6.2 Å |
構造データ | EMDB-16398, PDB-8c2s: EMDB-16514: Cryo-EM structure of NDUFS4 knockout of respiratory complex I from Mus musculus kidney. EMDB-16515, PDB-8ca1: EMDB-16516, PDB-8ca3: EMDB-16517, PDB-8ca4: EMDB-16518, PDB-8ca5: |
化合物 | ChemComp-SF4: ChemComp-PC1: ChemComp-FES: ChemComp-FMN: ChemComp-3PE: ChemComp-CDL: ChemComp-LMT: ChemComp-GTP: ChemComp-NAP: ChemComp-ZN: ChemComp-EHZ: ChemComp-FAD: ChemComp-UQ9: ChemComp-NDP: |
由来 |
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キーワード | OXIDOREDUCTASE / NADH ubiquinone oxidoreductase / Complex I |