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.