Understanding mitochondrial complex I assembly in health and disease
journal contributionposted on 2012-06-01, 00:00 authored by Masakazu Mimaki, Xiaonan Wang, Matthew McKenzieMatthew McKenzie, David R Thorburn, Michael T Ryan
Complex I (NADH:ubiquinone oxidoreductase) is the largest multimeric enzyme complex of the mitochondrial respiratory chain, which is responsible for electron transport and the generation of a proton gradient across the mitochondrial inner membrane to drive ATP production. Eukaryotic complex I consists of 14 conserved subunits, which are homologous to the bacterial subunits, and more than 26 accessory subunits. In mammals, complex I consists of 45 subunits, which must be assembled correctly to form the properly functioning mature complex. Complex I dysfunction is the most common oxidative phosphorylation (OXPHOS) disorder in humans and defects in the complex I assembly process are often observed. This assembly process has been difficult to characterize because of its large size, the lack of a high resolution structure for complex I, and its dual control by nuclear and mitochondrial DNA. However, in recent years, some of the atomic structure of the complex has been resolved and new insights into complex I assembly have been generated. Furthermore, a number of proteins have been identified as assembly factors for complex I biogenesis and many patients carrying mutations in genes associated with complex I deficiency and mitochondrial diseases have been discovered. Here, we review the current knowledge of the eukaryotic complex I assembly process and new insights from the identification of novel assembly factors. This article is part of a Special Issue entitled: Biogenesis/Assembly of Respiratory Enzyme Complexes.
JournalBiochimica et biophysica acta (BBA) - bioenergetics
Pagination851 - 862
LocationAmsterdam, The Netherlands
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Publication classificationC1.1 Refereed article in a scholarly journal
Copyright notice2011, Elsevier B.V.
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MitochondriaRespiratory chainComplex IComplex I deficiencyAssembly factorAcyl-CoA DehydrogenasesAnimalsElectron Transport Complex IMitochondrial DiseasesMitochondrial ProteinsNADH DehydrogenaseOxidative PhosphorylationProtein MultimerizationProtein Structure, QuaternaryProtein SubunitsScience & TechnologyLife Sciences & BiomedicineBiochemistry & Molecular BiologyBiophysicsAPOPTOSIS-INDUCING FACTORNADH-UBIQUINONE OXIDOREDUCTASEHEREDITARY OPTIC NEUROPATHYBOVINE HEART-MITOCHONDRIACYTOCHROME-C-OXIDASENUCLEAR-ENCODED SUBUNITSLEIGH-SYNDROMEOXIDATIVE-PHOSPHORYLATIONDNA MUTATIONNEUROSPORA MITOCHONDRIA