microRNA-378 promotes autophagy and inhibits apoptosis in skeletal muscle

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
DOI: 10.1073/pnas.1803377115 Publication Date: 2018-10-29T19:09:08Z
ABSTRACT
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.
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