Assembly factors of human mitochondrial complex I and their defects in disease.
NADH-ubiquinone oxidoreductase (complex I) is a large, multimeric enzyme complex involved in the generation of ATP by oxidative phosphorylation. Complex I is comprised of 45 subunits which must be assembled together in a coordinated process to form the mature holoenzyme. In recent years, much progress has been made into understanding how complex I is assembled and the work provides potential insights into the biogenesis of other multisubunit membrane complexes. For complex I assembly to proceed effectively, a group of proteins termed "assembly factors" are required. A number of these assembly factors have now been identified and characterized; however, their exact roles in complex I biogenesis are not yet fully understood. This review summarizes the current model of human complex I assembly and the roles played by different assembly factors at early, mid, and late assembly stages. Defects in assembly factors which disrupt complex I assembly and contribute to human disease pathogenesis will also be discussed.
Mckenzie
Matthew
M
Department of Biochemistry, La Trobe University, Melbourne, VIC, Australia. M.McKenzie@latrobe.edu.au
Ryan
Michael T
MT
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D051033:Apoptosis Inducing Factor / Q000502:physiology; D004272:DNA, Mitochondrial / Q000502:physiology; D042967:Electron Transport Complex I / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics*; D006801:Humans; D008780:Methyltransferases / Q000502:physiology; D008928:Mitochondria / Q000235:genetics; D024101:Mitochondrial Proteins / Q000502:physiology; D018832:Molecular Chaperones / Q000502:physiology; D009245:NADH Dehydrogenase / Q000502:physiology; D043583:Nucleoside-Triphosphatase / Q000502:physiology
C494829:AIFM1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D051033:Apoptosis Inducing Factor; D004272:DNA, Mitochondrial; C518657:Ecsit protein, human; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; C501824:NDUFAF2 protein, human; C541710:NDUFAF3 protein, human; C530233:NDUFAF6 protein, human; D009245:NADH Dehydrogenase; D008780:Methyltransferases; C532992:NDUFAF5 protein, human; D043583:Nucleoside-Triphosphatase; D042967:Electron Transport Complex I; C506342:NDUFAF1 protein, human