Loss of Muscle MTCH2 Increases Whole-Body Energy Utilization and Protects from Diet-Induced Obesity

Mitochondrial carrier homolog 2 (MTCH2) is a repressor of mitochondrial oxidative phosphorylation (OXPHOS), and its locus is associated with increased BMI in humans. Here, we demonstrate that mice deficient in muscle MTCH2 are protected from diet-induced obesity and hyperinsulinemia and that they demonstrate increased energy expenditure. Deletion of muscle MTCH2 also increases mitochondrial OXPHOS and mass, triggers conversion from glycolytic to oxidative fibers, increases capacity for endurance exercise, and increases heart function. Moreover, metabolic profiling of mice deficient in muscle MTCH2 reveals a preference for carbohydrate utilization and an increase in mitochondria and glycolytic flux in muscles. Thus, MTCH2 is a critical player in muscle biology, modulating metabolism and mitochondria mass as well as impacting whole-body energy homeostasis.

Errata: In the originally published version of this article, there was a mistake in Figure S1B: the two fields originally presented were adjacent views of the same gastrocnemius muscle sample. At the time of image acquisition, the images presented in the paper were mislabeled. To correct for this mistake, the authors returned to the original slides (prepared at the original time of collection; prior to publication) and chose two different experiments containing three mice from each genotype (a total of six mice/slides) and acquired images of each. The authors have used these pictures to prepare a corrected version of Figure S1, which has now been corrected online and appears below.