Apoptosis in skeletal muscle and its relevance to atrophy

Abstract

Apoptosis is necessary for maintaining the integrity of proliferative tissues, such as epithelial cells of the gastrointestinal system. The role of apoptosis in post mitotic tissues, such as skeletal muscle, is less well defined. Apoptosis during muscle atrophy occurs in both myonuclei and other muscle cell types. Apoptosis of myonuclei likely contributes to the loss of muscle mass, but the mechanisms underlying this process are largely unknown. Caspase-dependent as well as -independent pathways have been implicated and the mode by which atrophy is induced likely determines the apoptotic mechanisms that are utilized. It remains to be determined whether a decrease in apoptosis will alleviate atrophy and distinct research strategies may be required for different causes of skeletal muscle loss.

Figure 1

Pathways involved in apoptosis in skeletal muscle. Caspase-dependent and -independent pathways are likely involved in apoptotic nuclear loss during atrophy in skeletal muscle. Caspase-3 activation and subsequent apoptosis occurs through the release of cytochrome-c from mitochondria in response to changes in the ratio of pro- and anti-apoptotic members of the Bcl-2 family of proteins, or through the activation of initiator caspases, such as caspase-8 or -12. Caspase-independent pathways such as the release of EndoG and/or AIF may be more important in skeletal muscle as they directly induce DNA fragmentation.