Mitochondrial biogenesis in health and disease. Molecular and therapeutic approaches.

Mitochondrial biogenesis (MB) is the essential mechanism by which cells control the number of mitochondria. Cells respond to different physiologic, metabolic, and pathologic changes by regulating this organelle with high morphological and functional adaptability. A considerable number of proteins, transcription factors, upstream regulatory proteins and secondary mechanisms are involved in MB and the stabilization of new mitochondrial DNA. These MB activators and regulators, including the main participating proteins (e.g. PGC-1α and mtTFA), are candidates for therapeutic intervention in diverse diseases, like neurodegenerative disorders, metabolic syndrome, sarcopenia, cardiac pathophysiology and physiological processes like aging. In this review, we analyze the implication of MB in several diseases in which the MB pathway is affected. Furthermore, we describe therapeutical interventions on MB targets to boost MB for the prevention and treatment of human diseases. Furthermore, evidence based results and the knowledge gained during last years for some of these drugs aim us hypothesize about the value of a given treatment involved in the activation of MB.