Metabolic inflexibility has been implicated in the pathogenesis of obesity and the development of insulin resistance. Tarpey et al. observed elevated markers of mitophagy activity in skeletal muscle of endurance-trained runners (ET) compared with sedentary (SED) males, without a discernible difference in markers of autophagy. However, the greater content of mitophagy markers in skeletal muscle of ET individuals was not associated with a corresponding higher level of metabolic flexibility. Still, skeletal muscle metabolic flexibility increased following a high-fat meal in the ET but not SED individuals.