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Daily Heat Stress Treatment Normalizes Denervation‐Activated Autophagy and Mitophagy in Mouse Skeletal Muscle
Author(s) -
Tamura Yuki,
Kitaoka Yu,
Matsunaga Yutaka,
Hoshino Daisuke,
Hatta Hideo
Publication year - 2015
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.29.1_supplement.821.2
Subject(s) - autophagy , mitophagy , microbiology and biotechnology , parkin , ulk1 , mtorc1 , chemistry , integrated stress response , ampk , pink1 , muscle atrophy , sdha , skeletal muscle , pi3k/akt/mtor pathway , biology , mitochondrion , signal transduction , endocrinology , medicine , phosphorylation , biochemistry , protein kinase a , messenger rna , apoptosis , translation (biology) , succinate dehydrogenase , disease , parkinson's disease , gene
It has been considered that heat stress treatment is a beneficial strategy to counter disuse‐induced muscle wasting. However, its underlying molecular mechanisms remains unclear. Because recent studies demonstrate that excessive activation of autophagy and mitophagy are key mediators of muscle atrophy, we examined the effects of heat stress treatment (exposing mice to hot environment chamber; 40 ºC, 30 min/day, 7 days) on autophagic and mitophagic signaling during experimental disuse (sciatic nerve transection for 10 days) in gastrocnemius muscle. We herein report that heat stress normalized denervation‐upregulated the proteins expression related to autophagy (P62/UQCRC2 and LC3‐II) and mitophagy (Parkin, Ubiquitin‐conjugated, P62/SQSTM1, and LC3‐II in mitochondrial fraction). These observations were also reproduced in experiment with colchicine which is an inhibitor of autophagosome and mitophagosome degradation, indicating heat stress attenuates the induction step of autophagy and mitophagy but not accelerates the final clearance step. Interestingly, heat stress did not affect the initial cellular signaling of autophagy induction/suppression (phosphorylated form and total expression of AMPK, mTORC1, and ULK1). Therefore, it suggests that the normalization of autophagy and mitophagy induction by heat stress could be via suppression of some intermediate steps of autophagy. Our current observations contribute to better understanding of autophagy and mitophagy regulations from the translational perspective.