Assembly Factors of Human Mitochondrial Complex I and Their Defects in Disease

NADH-ubiquinone oxidoreductase (complex 1) 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 1 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 1 assembly and the roles played by different assembly factors at early, mid, and late assembly stages. Detects in assembly factors which disrupt complex I assembly and contribute to human disease pathogenesis will also be discussed. (C) 2010 IUBMB IUBMB Life, 62(7): 497-502, 2010