Protein α-actinin-3 is a major component of fast-twitch muscle fibers. Elite endurance athletes commonly have mutations that result in the loss of that protein. Loss of α-actinin-3 is associated with reduced power, increased endurance capacity, and enhanced response to endurance training.
In this issue of the Journal of Clinical Investigation
, Kathryn North and colleagues at the Murdoch Children's Research Institute report that the loss of α-actinin-3 in fast-twitch muscle fibers, results in compensation by α-actinin-2. The presence of α-actinin-2 in fast-twitch muscle contributed to reprogramming these muscles through increased calcineurin signaling. This study provides insight into how mutations in the gene encoding α-actinin-3 promote skeletal muscle adaptations that are advantageous to elite endurance athletes.