Editorial: Autophagy and Mitophagy in Skeletal Muscle Health and Disease

Abstract

Editorial on the Research Topic Autophagy and Mitophagy in Skeletal Muscle Health and Disease This Research Topic is dedicated to explorations of the functional roles of autophagy and mitophagy in skeletal muscles at molecular, cellular, and physiological levels. Autophagy is the cell's own waste management plant, where unneeded or dysfunctional components of the cell are disposed of or recycled. It is an orderly system, but extremely complex. There are several specialized structures and a wide array of regulatory molecules involved in autophagy. It plays a number of different functional roles depending on whether it is doing general housekeeping, assisting in host defense, reacting to cellular stress, taking part in embryonic development, or controlling the existential task of managing cell survival and cell death. The collection of papers we have assembled therefore covers a wide range of topics, including an examination of lysosomal enzyme activity in skeletal muscle cells, an inquiry into the effects of exercise on autophagic signaling pathways, a comparison of how mitophagy is regulated in non-muscle cell lines vs. skeletal muscles, an investigation into how sympathetic innervation regulates autophagy, and an overview of how autophagy maintains muscle cell homeostasis under physiological and pathological conditions. AUTOPHAGY IN SKELETAL MUSCLES Skeletal muscle mass depends on a balance between protein synthesis and protein degradation. When muscle tissues are in a catabolic state, enhanced protein degradation leads to loss of muscle mass, a condition known as atrophy (Bonaldo and Sandri, 2013). Four proteolytic pathways govern this degradation process: the calpain, caspase, ubiquitin-proteasome, and autophagy-lysosomal pathways. In this Research Topic, we focus on the last one, the autophagy system, where cytosolic components and organelles are degraded by lysosomes. While four forms of autophagy have thus far been identified, for the present purposes, the term autophagy is synonymous with macroautophagy, which is the predominant form and the one that has been most thoroughly described in skeletal muscle physiology. Autophagy is initiated by the ULK1 complex and a BECLIN1-dependent phagophore nucleation process follows, resulting in activation of local PI3P production. PI3P recruits the ATG protein WIPI2 and the ER-localized protein DFCP1 to the omegasome (a subdomain of the endoplasmic reticulum). WIPI2 binds directly to ATF16L1, triggering the ATG12-ATG5-ATF16L1 complex to