Exercise

Science 20 January 2012: 
Vol. 335 no. 6066 p. 281 
DOI: 10.1126/science.335.6066.281

• NEWS FOCUS

AUTOPHAGY

Explaining Exercise

1. Ken Garber*

Exercise has many benefits, but the mechanisms behind them remain murky. Because autophagy’s recycling of cellular contents helps cells meet energy demands, researchers wondered whether exercise triggers autophagy and if that could somehow account for exercise’s benefits. In the December issue of Autophagy, an Italian research team reported the first evidence that exercise induces autophagy in the skeletal muscles of mice. This week in Nature, other researchers confirm that observation and extend it much further, documenting that autophagy is required for exercise’s beneficial metabolic effects./.../

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 Bassel-Duby,
• Philipp E. Scherer
• &Beth Levine

Nature
 
(2012)
 
doi:10.1038/nature10758

Received

 

22 September 2010 

Accepted

 

06 December 2011 

Published online

 

18 January 2012

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Exercise has beneficial effects on human health, including protection against metabolic disorders such as diabetes¹. 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 control². During stress, increased levels of autophagy permit cells to adapt to changing nutritional and energy demands through protein catabolism³. Moreover, in animal models, autophagy protects against diseases such as cancer, neurodegenerative disorders, infections, inflammatory diseases, ageing and insulin resistance^4, 5, 6. 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./.../