Mitochondrial Complex I Deficiency in Humans

Abstract : The mechanism of NADH oxidation varies between living organisms, and is by far the most complex oxidizingsystem found in mitochondria. In human mitochondria, a unique, but huge structure, with more than 45 subunits, knownas complex I, copes with NADH oxidation. This review compiles our present knowledge on the organization of thiscomplex and the putative role of a small subset of its subunits. This review also describes the major progress that has beenmade in understanding the molecular bases of respiratory chain complex I deficiency in humans, with mutations identifiedin both the mitochondrial and the nuclear genes encoding complex I subunits. Finally, the puzzling questions raised by thevarying clinical presentations of patients with complex I deficiency are discussed in light of our limited knowledge oncomplex I function in mammalian cells. Key Words: Mitochondria, Respiratory Chain, Complex I deficiency, NADH. MITOCHONDRIAL OXIDATION OF REDUCEDNICOTINAMIDE ADENINE DINUCLEOTIDES:FROM THE MANY DEHYDROGENASES OF PLANTSTO THE UNIQUE MAMMALIAN COMPLEX I

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