Premium
Autophagy and mitophagy flux in skeletal muscle during chronic‐contractile activity
Author(s) -
Kim Yuho,
Triolo Matthew,
Erlich Avigail,
Lai Jenny,
Hood David A.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.857.6
Subject(s) - autophagy , mitophagy , tfeb , skeletal muscle , chemistry , medicine , endocrinology , colchicine , mitochondrion , downregulation and upregulation , bafilomycin , flux (metallurgy) , biology , biochemistry , apoptosis , organic chemistry , gene
Autophagy and mitophagy are important cellular recycling mechanisms, however the regulation of autophagy and mitophagy flux in training‐induced muscle adaptations remains to be elucidated. Using the microtubule destabilizer colchicine (0.04 mg/kg), this study assessed LC3II and p62 flux in skeletal muscles of Sprague‐Dawley rats (501 ± 9 g) subjected to chronic contractile activity (CCA; 3 hours/day, 9V, 10 Hz continuous, 0.1 ms pulse duration) for 1, 2, 3, 5, and 7 days (N=6–8/group). Colchicine was given via an intraperitoneal injection 48 hours prior to tissue collection, whereas control animals were administered saline as a vehicle treatment. Following 7 days of CCA, there were significant increases in maximal state 3 respiration, accompanied by a decrease in ROS production in IMF mitochondria ( P < 0.05), indicating that mitochondrial adaptations were elicited in the stimulated muscle. Notably, whole muscle autophagy flux, as measured by LC3II and p62, was downregulated in response to 3 days of CCA, and further by 7 days of CCA ( P < 0.05). In addition, muscle mitochondrial LC3II flux was decreased by 3 days of CCA, indicative of reduced mitophagy. In contrast, the lysosomal system, measured by TFEB and LAMP1 protein levels, was gradually upregulated by CCA, culminating at day 7. Interestingly, the translocation of TFEB into the nucleus in response to CCA was increased at day 3 ( P < 0.05). However, this nuclear TFEB was not sustained and subsequently declined back to basal levels. In conclusion, we suggest that chronic exercise can lead to muscle adaptations through a coordinated mechanism, involving a decrease in autophagy/mitophagy flux, combined with an increase in the capacity of the lysosomal system. Support or Funding Information This work was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .