Exercise-conditioned serum drives mitochondrial remodeling in neurons

Exercise and fasting strategies are linked to improved brain health. Despite this little is known about how these interventions affect neuronal mitochondrial quality control. We hypothesized that circulating factors induced by acute exercise could stimulate neuronal mitochondrial quality control. To test this hypothesis, we treated primary cortical mouse neurons with serum collected from C57Bl/6J mice immediately following a single bout of exhaustive treadmill running or from sedentary controls. Neurons exposed to exercise serum exhibited increased markers of mitochondrial biogenesis and mitophagy. Proteomics analysis of exercise serum-treated neurons revealed changes in mitochondrial and autophagy-related proteins and upregulation of mitochondrial biogenesis, protein quality control, and redox signaling pathways. To determine if one bout of exercise activates brain mitophagy in vivo, we subjected mice to an acute fasting and treadmill running paradigm followed by electron microscopy of the frontal cortex. Acute exercise in a fasted state increased mitophagy structures. These results demonstrate that circulating factors induced by acute exercise promote mitophagy and mitochondrial turnover in neurons.