Respiratory chain complex I deficiency

Oxidative phosphorylation disorders make a contribution of 1 per 10,000 liv e births in man, of which isolated complex I deficiency is frequently the c ause. Complex I, or NADH:ubiquinone oxidoreductase, is the largest multi-pr otein enzyme complex of the mitochondrial electron transfer chain. In compl ex I deficiency, various clinical phenotypes have been recognized, often re sulting in multi-system disorders with a fatal outcome at a young age. Rece nt advances in complex I deficiency, regarding clinical, biochemical, and m olecular aspects are described. However, the genetic causes of about 60% of complex I deficiency remain unclear. As a consequence, further research wi ll be needed to clarify the genetic defects in the remaining cases. Novel s trategies in which interesting non-structural nuclear-encoded disease-causi ng genes may be found, as well as the molecular genetic composition of huma n complex I, are presented. (C) 2001 Wiley-Liss, Inc.