Aim: The diseases of the oxidative phosphorylation system consist of a group of disorders originated by a deficient synthesis of adenosine triphosphate (ATP). These diseases are increasingly being diagnosed among patients with multisystemic disorders. Mitochondrial deoxyribonucleic acid (mtDNA) mutations are usually maternally inherited, but they also can be sporadic or secondary to nuclear mutations, that are inherited in a Mendelian mode, or due to environmental hazards. In this review we will update, from a genetic point of view, the knowledge on human mitochondrial diseases, remarking the difficulties to study these pathologies.
Development: To mirror these difficulties, we will use selected examples of mutations in the mitochondrial genome, and review recent advances on mitochondrial pathology due to mutations in the nuclear genes codifying for mitochondrial proteins that participate in a good performance of the oxidative phosphorylation system.
Conclusions: Sequencing of the complete human mtDNA should be part of the basic profile in the study of mitochondrial diseases. Due to the increasing number of nuclear genes involved in the oxidative phosphorylation system performance, their analysis should be based on solid biochemical clues.