The Role of ATF5 in Mitochondrial Maintenance, Biogenesis and UPRmt Signaling Following Acute Exercise in Skeletal Muscle

Maintenance of the mitochondrial protein folding environment is essential for organellar and cellular homeostasis. The Mitochondrial Unfolded Protein Response (UPRmt) is a protein quality control mechanism that relieves intraorganellar proteotoxic stress in a manner dependent on activating transcription factor 5 (ATF5) during mitochondrial dysfunction. Protein homeostasis can temporarily be disrupted by acute exercise, inducing the UPRmt. Using WT and whole-body ATF5 KO animals, we sought to determine the role of ATF5 in regulating basal mitochondrial content and function, in addition to acute exercise-induced changes in UPRmt signaling. Our data reveal that ATF5 is required in the maintenance of a high-quality mitochondrial pool and mediating the transcription of UPRmt genes during exercise. However, the specific mechanisms by which ATF5 and the UPRmt coordinate the preservation of mitochondrial homeostasis and whether they are required in mediating mitochondrial adaptations to chronic exercise are avenues of future work.