Grant: Operating Grant

Mitochondria play many important roles in cellular homeostasis. They are involved in energy production through oxidative phosphorylation and beta-oxidation of fatty acids, in initiation of the intrinsic pathway of apoptosis and in calcium homeostasis modulation. Recently, the importance of maintaining protein quality control in this organelle has been demonstrated by the identification of diseases associated with members of this control system. Interestingly, organisms having an enhanced protein quality control system tend to have an increased longevity and an enhanced resistance to stress. As mitochondria are key players in different important cellular processes and since the lost of their integrity can have severe cellular consequences and is linked to aging and neurological disorders in human, we will investigate the modulation and the mechanisms of the mitochondrial protein quality control system during lifespan and validate them in a disease model, Freidreich ataxia. In addition to unveiling hidden facets of protein maintenance in mitochondria, the work should highlight new ways to fight against diseases involving mitochondrial dysfunction defective protein folding and suggest alternative therapeutics for slowing of the aging process.