Type 2 fibers are more prone to mitochondrial failure because they have lower mitochondrial content and lower oxidative capacity being fast-twitch fibers that rely on glycolysis, and exhibit lower expression of E3 Ub-ligases and proteasome-mediated protein degradation.46 CCO negative fibers in IBM have also been shown to have increased mitochondrial DNA mutation loads.16 Moreover, the predilection of type 2 fibers also raises suspicion for underlying metabolic disturbances, which has not yet been fully explored in IBM. This evidence concerns the gene RYR1 and inclusion body myositis.