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Acute Endurance Exercise‐mediated Autophagy Occurs in Parallel with The Simultaneous Activation of mTOR
Author(s) -
Lee Youngil,
Cho Joonyong,
Cho InHo,
Kang Eunbum,
Javan Gulnaz,
Cosio Lima Ludmila
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.821.5
Subject(s) - autophagy , pi3k/akt/mtor pathway , endurance training , chemistry , medicine , microbiology and biotechnology , apoptosis , biology , biochemistry
Endurance exercise (EE) is a strong inducer of autophagy in the heart. However, the exact mechanisms responsible for exercise‐induced cardiac autophagy remain unclear. Here we showed that acute EE induces autophagy despite the mTOR activation. C57BL/6 mice were randomly assigned to either exercise (n=7) or sedentary group (n=7). After acclimatization, mice were trained for 60 min on a motorized treadmill at 12m/min on a 0% grade. Hearts were excised immediately 1‐hour post exercise and homogenized for Western blot analyses. We found that EE significantly increased autophagy (an increase in the ratio of LC3II to LC3I and a reduction in P62) without changes in the levels of Beclin 1; however, ATG7 essential for autophagsome formation was highly increased compared to the sedentary group. Intriguingly, in contrast to the canonical autophagy pathway, EE promoted autophagy in parallel with mTOR activation. Accordingly, we measured both upstream (Akt) and downstream p70s6k) signaling of mTOR, respectively and confirmed that levels of phosphorylation of both Akt and p70s6k were increased. AMPK is a potent inducer of autophagy. We observed that EE augmented AMPK phosphorylation. A BH3‐only protein, BNIP3 is also linked to autophagy, and its expression is regulated by a transcription factor, hypoxia inducing factor 1 (HIF1). Our data showed that EE increased both HIF1 and BNIP3. Taken together, our results suggest for the first time that acute EE induces autophagy in a Beclin1 and mTOR independent manner and that EE‐induced activation of cell survival signaling does not interfere in autophagy flux.