Regulation of the autophagy system during chronic contractile activity‐induced muscle adaptations. Issue 14 (18th July 2017)

• Record Type: Journal Article
• Authors: Kim, Yuho; Hood, David A.
• Is Part Of: Physiological reports. Volume 5:Issue 14(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-07-18
• Subjects: Autophagy -- exercise -- lysosome -- mitochondrial biogenesis; Physiology -- Periodicals; 571
• DOI: 10.14814/phy2.13307
• Languages: English
• ISSNs: 2051-817X

Abstract

Abstract: Skeletal muscle is adaptable to exercise stimuli via the upregulation of mitochondrial biogenesis, and recent studies have suggested that autophagy also plays a role in exercise‐induced muscle adaptations. However, it is still obscure how muscle regulates autophagy over the time course of training adaptations. This study examined the expression of autophagic proteins in skeletal muscle of rats exposed to chronic contractile activity (CCA; 6 h/day, 9V, 10 Hz continuous, 0.1 msec pulse duration) for 1, 3, and 7 days ( n = 8/group). CCA‐induced mitochondrial adaptations were observed by day 7, as shown by the increase in mitochondrial proteins (PGC‐1α, COX I, and COX IV), as well as COX activity. Notably, the ratio of LC3 II/LC3 I, an indicator of autophagy, decreased by day 7 largely due to a significant increase in LC3 I. The autophagic induction marker p62 was elevated on day 3 and returned to basal levels by day 7, suggesting a time‐dependent increase in autophagic flux. The lysosomal system was upregulated early, prior to changes in mitochondrial proteins, as represented by increases in lysosomal system markers LAMP1, LAMP2A, and MCOLN1 as early as by day 1, as well as TFEB, a primary regulator of lysosomal biogenesis and autophagy flux. Our findings suggest that, in response to chronic exercise, autophagy is upregulated concomitant with mitochondrial adaptations. Notably, our data reveal the surprising adaptive plasticity of the lysosome in response to chronic contractile activity which enhances muscle health by providing cells with a greater capacity for macromolecular and organelle turnover. Abstract : In this manuscript, we show that lysosomes are inducible by chronic exercise in skeletal muscle. This will enhance the capacity of the muscle for autophagic flux and represents an adaptation that can counter lysosomal storage diseases.