The Unfolded Protein Response in Relation to Mitochondrial Biogenesis in Skeletal Muscle Cells

Mitochondrial biogenesis involves nuclear- and mitochondrial-derived proteins to be integrated into functional organelles. Muscle development and chronic exercise are two physiological stimuli that trigger the production of mitochondrial components to produce more mitochondria. However, the synthesis of new proteins can induce cellular stress. Thus, the unfolded protein response (UPR), which takes place in the mitochondria or the endoplasmic reticulum, ensures correct protein handling. Whether the UPR must precede mitochondrial biogenesis is unknown. We used two models of mitochondrial biogenesis, skeletal muscle differentiation and chronic exercise of muscle cells in culture, and examined UPR activation. We partially inhibited one branch of the UPR involving the protein CHOP, with either a drug (TUDCA) or gene knockdown. Our results indicate that mitochondrial biogenesis occurs independently of stress-induced CHOP, and reducing ER stress may further augment mitochondrial content.