Molecular mechanism of exercise training-induced skeletal muscle adaptation (Learn more)
Mitochondrion, the power plant in the cell, is a dynamic organelle that plays critical roles in metabolism and disease. Research in this laboratory has focused on two opposite processes: addition (mitochondrial biogenesis) and removal (mitophagy) of mitochondria in skeletal muscle. We have revealed that mitogen-activated protein kinase (MAPK) p38γ isoform, but not p38α or p38b isoform, is critical for exercise training-induced mitochondrial biogenesis through peroxisome proliferator activated receptor γ co-activator-1α (Pgc-1α). We are ascertaining the isoform-specific p38 signaling and function in contractile and metabolic functions (NIH R01 supported). We also found that exercise training promotes mitophagy. We now study the functional importance of exercise training-induced mitophagy in metabolic and contractile adaptations, focusing on autophagy related genes, Atg1, Atg6 and Atg7 (ADA Basic Research Award). Meanwhile, we have developed a novel mitochondrial reporter gene, MitoTimer, for mitochondrial quantity and quality, and we are developing conditional transgenic MitoTimer reporter mice for assessing mitochondrial quantity and quality in vivo. (NIH R21 pending). Using this technology, we currently study the exercise impacts on mitochondria and muscle function in Friedreich's ataxia (FA) (funded by FARA). An improved understanding of mitochondrial maintenance and remodeling in skeletal muscle will facilitate the development of new interventions for numerous medical conditions, such as FA heart failure, cachexia and type 2 diabetes.