microRNA-378 promotes autophagy and inhibits apoptosis in skeletal muscle

• DOI: 10.1073/pnas.1803377115
• Publication Date: 2018-10-29T19:09:08Z
• Authors: Yan Li; Jingjing Jiang; Wei Liu; Hui Wang; Lei Zhao; Shengnan Liu; Peng Li; Shengjie Zhang; Chao Sun; Yuting Wu; Shuxian Yu; Xihua Li; Hui Zhang; Haifeng Qian; Duo Zhang; Feifan Guo; Qiwei Zhai; Qiurong Ding; Li Wang; Hao Ying
• Keywords: Male; Mice, Knockout; 0301 basic medicine; Muscle Cells; Forkhead Box Protein O1; TOR Serine-Threonine Kinases; Apoptosis; Caspase 9; Running; 3-Phosphoinositide-Dependent Protein Kinases; Mice; MicroRNAs; 03 medical and health sciences; Stress, Physiological; Autophagy; Animals; Autophagy-Related Protein-1 Homolog; 14. Life underwater; Muscle, Skeletal; Signal Transduction

Significance Muscle wasting and weakness can be observed under either physiological or pathological conditions, which are partly due to an imbalance between autophagy (“self-eating”) and apoptosis (“self-killing”). How microRNAs coordinate autophagy and apoptosis in the metabolic regulation of cell death remains largely unknown. This work identifies miR-378 as a critical component of metabolic checkpoints, which integrates metabolic information into an adaptive response to reduce the propensity of myocytes to undergo apoptosis by enhancing autophagy and suppressing apoptosis via directly targeting phosphoinositide-dependent protein kinase 1 and Caspase 9, respectively. Our study highlights a crucial role of miR-378 in maintaining normal muscle homeostasis by orchestrating autophagy and apoptosis processes and provides a potential therapeutic target to treat myopathies.