8c2s | pdb_00008c2s
Cryo-EM structure NDUFS4 knockout complex I from Mus musculus heart (Class 1).
Structural highlights
FunctionNDUV2_MOUSE Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone (By similarity). Publication Abstract from PubMedRespiratory 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. Structural insights into respiratory complex I deficiency and assembly from the mitochondrial disease-related ndufs4(-/-) mouse.,Yin Z, Agip AA, Bridges HR, Hirst J EMBO J. 2024 Jan;43(2):225-249. doi: 10.1038/s44318-023-00001-4. Epub 2024 Jan 2. PMID:38177503[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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