ROLE OF MITOCHONDRIAL METABOLISM ON THE PATHOPHYSIOLOGY OF SKELETAL MUSCLE

Our research focuses on understanding how mitochondrial bioenergetics contribute to various cellular functions. Mitochondrial metabolism goes beyond ATP production and plays roles in cell death control, immunity, and oncogenesis. Impaired mitochondrial function is linked to metabolic disorders. We study mitochondrial metabolism's role in skeletal muscle pathophysiology, particularly the formation of muscular tubular aggregates (TA) caused by chronic mitochondrial dysfunction. TA is associated with various disorders. We investigated the molecular mechanisms of TA formation and potential therapies using a mouse model. Chronic mitochondrial ATP synthase inhibition triggers TA formation, involving increased mitochondrial fission, mitophagy, and interactions with the sarcoplasmic reticulum. This leads to calcium buffering attempts. Hypoxia exacerbates TA formation, and edaravone treatment restores a healthy phenotype by promoting mitochondrial fusion and mitigating TA development.