Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis

Congcong He, Michael C. Bassik, Viviana Moresi, Kai Sun, Yongjie Wei, Zhongju Zou, Zhenyi An, Joy Loh, Jill Fisher, Qihua Sun, Stanley Korsmeyer, Milton Packer, Herman I. May, Joseph A Hill, Herbert W. Virgin, Christopher Gilpin, Guanghua Xiao, Rhonda S Bassel-Duby, Philipp E Scherer, Beth Levine

Research output: Contribution to journalArticlepeer-review

881 Scopus citations


Exercise has beneficial effects on human health, including protection against metabolic disorders such as diabetes. However, the cellular mechanisms underlying these effects are incompletely understood. The lysosomal degradation pathway, autophagy, is an intracellular recycling system that functions during basal conditions in organelle and protein quality control. During stress, increased levels of autophagy permit cells to adapt to changing nutritional and energy demands through protein catabolism. Moreover, in animal models, autophagy protects against diseases such as cancer, neurodegenerative disorders, infections, inflammatory diseases, ageing and insulin resistance. Here we show that acute exercise induces autophagy in skeletal and cardiac muscle of fed mice. To investigate the role of exercise-mediated autophagy in vivo, we generated mutant mice that show normal levels of basal autophagy but are deficient in stimulus (exercise-or starvation)-induced autophagy. These mice (termed BCL2 AAA mice) contain knock-in mutations in BCL2 phosphorylation sites (Thr69Ala, Ser70Ala and Ser84Ala) that prevent stimulus-induced disruption of the BCL2-beclin-1 complex and autophagy activation. BCL2 AAA mice show decreased endurance and altered glucose metabolism during acute exercise, as well as impaired chronic exercise-mediated protection against high-fat-diet-induced glucose intolerance. Thus, exercise induces autophagy, BCL2 is a crucial regulator of exercise-(and starvation)-induced autophagy in vivo, and autophagy induction may contribute to the beneficial metabolic effects of exercise.

Original languageEnglish (US)
Pages (from-to)511-515
Number of pages5
Issue number7382
StatePublished - Jan 26 2012

ASJC Scopus subject areas

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