A B S T R A C T
The key role of mitochondria in oxidative metabolism and redox homeostasis explains the link between mitochondrial dysfunction and the development of metabolic disorders. Mitochondria’s highly dynamic nature,
based on alterations in biogenesis, mitophagy, fusion and fission, allows adjusting sequential redox reactions of
the electron transport chain (ETC) and dissipation of the membrane potential by ATP synthase, to different
environmental cues. With reactive oxygen species being an inevitable by-product of oxidative phosphorylation
(OXPHOS), alterations on mitochondrial oxidative rate with a consequent excessive load of reactive oxygen
species have been traditionally associated with pathological conditions. However, reactive oxygen species have
also been suggested as promoters of mitohormesis, a process in which low, non-cytotoxic concentrations of
reactive oxygen species promote mitochondrial homeostasis. Therefore, signaling systems involved in the regulation
of mitochondrial homeostasis are attractive candidates for drug development for metabolic diseases triggered by mitochondrial dysfunction. Reversible phosphorylation downstream the cyclic AMP (cAMP) signaling cascade and deacetylation mediated by sirtuins are recognized as major mitochondrial regulators.
Download: 2019_Mitohormesis and metabolic health