The invention relates to a method for combating disorders affecting the mitochondrial oxidative phosphorylation system by allotopic expression of the cyanide-insensitive alternative oxidase (AOX) in human cells. The successful expression of AOX in human cells and in Drosophila has been shown to confer spectacular cyanide-resistance to mitochondrial substrate oxidation, alleviate oxidative stress, apoptosis susceptibility and metabolic acidosis. AOX is well tolerated when expressed ubiquitously in the whole organism. AOX expression is a valuable tool to limit the deleterious consequences of respiratory chain deficiency.