Autophagy, a highly regulated intracellular system essential to skeletal muscle homeostasis : role in disease, exercise and altitude exposure
Résumé
Autophagy is an evolutionarily conserved intracellular system that selectively eliminates protein aggregates, damaged organelles, and other cellular debris. It is a self-cleaning process critical for cell homeostasis in conditions of energy stress. Autophagy has been until now relatively overlooked in skeletal muscle, but recent
data highlight its vital role in this tissue in response to several stress conditions. The most recognized sensors for autophagy modulation are the adenosine monophosphate (AMP)-activated protein kinase (AMPK) and the mechanistic target of rapamycin (MTOR). AMPK acts as a sensor of cellular energy status by regulating several intracellular systems including glucose and lipid metabolisms and mitochondrial biogenesis. Recently, AMPK has been involved in the control of protein synthesis by decreasing MTOR activity and in the control of protein breakdown programs. Concerning proteolysis, AMPK notably regulates autophagy through FoxO transcription
factors and Ulk1 complex. In this chapter, we describe the functioning of the different autophagy pathways (macroautophagy, microautophagy, and chaperonemediated autophagy) in skeletal muscle and define the role of macroautophagy in response to physical exercise, a stress that is well assumed to be a key strategy to counteract metabolic and muscle diseases. The effects of dietary factors and altitude exposure are also discussed in the context of exercise.