Structural insights into respiratory complex I deficiency and assembly from the mitochondrial disease-related ndufs4^-/- mouse.

ABSTRACT: 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

SUBMITTER: Yin Z 

PROVIDER: S-EPMC10897435 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature