Figure 1.

Link between autophagy and muscle regeneration. (A) Biological processes and related molecular mechanisms of classical degradative autophagy. (B) Inhibition of autophagy impairs skeletal muscle regeneration in animal models of muscle injury. As an inhibitor of PI3KC3, 3‐Methyladenine (3‐MA) can specifically block autophagosome formation. Treatment of myotoxic injury mice with 3‐MA resulted in decreased recovery of muscle strength and mitochondrial enzyme activity. Chloroquine (CQ) can inhibit the fusion of autophagosome and lysosome, thus blocking the autophagic flux. Similar to the results of 3‐MA, blocking the late process of autophagy with CQ also reduced the rate of regeneration with accumulation of sarcomere and nuclear debris. Skeletal muscle‐specific knockout of Ulk1, a kinase critical for autophagy initiation, attenuates the recovery of mitochondrial network and muscle strength in mice after muscle injury. In addition, genetic deletions of Atg5, Becn1, Atg16l, and Atg7 all lead to autophagy attenuation after muscle injury and impair muscle regeneration as well.