Grant: Master's Award: Canada Graduate Scholarships

Skeletal muscle fibres contain subpopulations of mitochondria that are responsive and adaptive to external stress-inducing stimuli, such as exercise. Mitochondria rely on constant and synchronized quality control processes, termed mitophagy (mitochondrial degradation), biogenesis (mitochondrial synthesis) and the mitochondrial unfolded protein response (UPRmt) to preserve cell homeostasis and function during stress-inducing conditions. Of particular interest, the UPR is a mitochondrial regulatory pathway which serves to mitigate the initial mitochondrial proteotoxicity caused by the accumulation of un-or-misfolded proteins within the mitochondria to restore cellular homeostasis. In our laboratory it has been suggested that the transcription factor ATF4 may play a possible role in mediating the UPRmt and in regulating mitochondrial adaptations during stress-inducing stimuli. The objectives of this project are to investigate the role of ATF4 in 1) mediating mitochondrial signaling with response to acute exercise, and 2) regulating mitochondrial adaptations in response to chronic exercise. To achieve these objectives, this study will subject Wild-Type and tamoxifen inducible ATF4 muscle-specific knockout mice to either a 6-week chronic exercise program, or to an acute bout of exercise. We hypothesize that ATF4 is required to mediate the UPRmt in response to both acute and chronic exercise-induced stress, and that the UPRmt induction is necessary for effective adaptation to exercise. Western Blot analyses of mitochondrial chaperones (HSP10, HSP60, HSP70). in response to acute and chronic exercise. The significance of this work will be to establish the role of ATF4 in promoting mitochondrial health and function during exercise.