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
The metabolic regulation of cell death is sophisticated. A growing body evidence suggests the existence multiple checkpoints that dictate fate in response to fluctuations. However, whether microRNAs (miRNAs) are able respond stress, reset threshold death, and attempt reestablish homeostasis largely unknown. Here, we show miR-378/378* KO mice cannot maintain normal muscle weight have poor running performance, which accompanied by impaired autophagy, accumulation abnormal mitochondria, excessive apoptosis skeletal muscle, whereas miR-378 overexpression enhance autophagy repress mice. Our vitro data stress-responsive promotes inhibits a cell-autonomous manner. Mechanistically, initiation through mammalian target rapamycin (mTOR)/unc-51-like activating kinase 1 (ULK1) pathway sustains via Forkhead box class O (FoxO)-mediated transcriptional reinforcement targeting phosphoinositide-dependent protein (PDK1). Meanwhile, suppresses intrinsic directly an initiator caspase-Caspase 9. Thus, propose critical component checkpoints, integrates information into adaptive reduce propensity myocytes undergo enhancing autophagic process blocking apoptotic initiation. Lastly, our suggest inflammation-induced down-regulation might contribute pathogenesis dystrophy.
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