Acute environmental hypoxia activates autophagy in human skeletal muscle (1167.2)

Abstract

Hypoxia‐induced muscle wasting is a phenomenon often described at high altitude, which has been attributed to an altered protein metabolism. We hypothesized that acute normobaric hypoxia would favour a negative net protein balance by repressing anabolic and activating proteolytic signaling pathways at rest and post‐exercise. Twenty‐two subjects participated in an experimental trial in normoxia and hypoxia (10.7% O2). Muscle biopsies were obtained before and after a 20‐min moderate exercise. In hypoxia, autophagic flux was increased as indicated by an increased LC3‐II/I ratio and LC3‐II expression and decreased p62/SQSTM1 expression. Following exercise in hypoxia a decrease in LC3‐I, LC3‐II and LC3‐II/I as well as in p62/SQSTM1 expressions was found. Bnip3 mRNA expression, a marker of mitophagy, was also increased in hypoxia. MAFbx mRNA expression, a muscle‐specific E3‐ligase, was increased in hypoxia and returned to levels similar to normoxia after exercise, while MuRF‐1 mRNA was not altered. In hypoxia, REDD1 expression and AMPK phosphorylation, two potential inhibitors of the PKB/mTOR pathway, were increased although phosphorylation of PKB, S6K1 and 4E‐BP1 was not modified. Our results indicate that environmental hypoxia modulates protein metabolism at rest and after moderate exercise by primarily altering protein breakdown, and more specifically the autophagy‐lysosomal system.