Denervation-induced oxidative stress and autophagy signaling in muscle

Alterations in contractile activity influence the intracellular homeostasis of muscle, which results in adaptations in the performance and the phenotype of this tissue. Denervation is an effective disuse model that functions to change the intracellular environment of muscle leading to a rapid loss in mass, a decrease in mitochondrial content, and an elevation in both proapoptotic protein expression and myonuclear apoptosis. Recent investigations have shown that alternative degradation pathways such as autophagy are activated in conjunction with apoptosis during chronic muscle disuse. We have previously shown that seven days of muscle disuse increases the expression of Beclin 1. Furthermore, we have also detected a significant increase in the expression of LC3-II, a known component of autophagy. In addition to its upregulation, denervation appears to induce the translocation of LC3-II to mitochondrial membranes. Collectively, these increases in protein expression suggest that autophagy signaling is upregulated in response to denervation, and that these pathways may preferentially target mitochondria for degradation in skeletal muscle.