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
AUTHORS (20)
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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CITATIONS (99)
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