The role of pexophagy in the maintenance of skeletal muscle mass

Peroxisomes are intracellular organelles involved in several cell functions such as lipid metabolism and reactive oxygen species clearance. Their abundance inside the cell is finely regulated through a balance between de novo biogenesis or division of existing organelles and a form of autophagic degradation called pexophagy. Skeletal muscle is the largest organ of the human body. Besides its well-known functions of locomotion, balance, respiration and eating, it actively participates in the regulation of whole-body metabolism. Previous studies have already shown that keeping a proper muscle mass significantly helps in maintaining a good health status. In contrast, several age-related conditions, including ageing sarcopenia, obesity, metabolic syndrome, and cancer, are characterized by muscle atrophy, leading to dramatic effects on health outcomes. Notably, peroxisome dysfunction has been implicated in these diseases, although the causal link between peroxisomal dysfunction and these pathologies remains elusive. Even-though peroxisomal functions in muscle are still poorly studied, previous work from our laboratory has shown that their dysfunction contributes to muscle atrophy in vivo. However, the precise molecular mechanisms are still under investigation. This thesis will discuss the role of peroxisomes in mammalian cells, and the effects of their selective elimination through pexophagy upon pharmacological induction, on the regulation and maintenance of muscle mass. Finally, this thesis will provide insights into possible future perspectives on the role of pexophagy in regulating skeletal muscle mass and related pathologies.