Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
Department of Veterinary Resources, Weizmann Institute of Science, Rehovot 76100, Israel.
Cell Rep. 2016 Feb 23;14(7):1602-1610. doi: 10.1016/j.celrep.2016.01.046. Epub 2016 Feb 11.
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.
线粒体载体家族 2 蛋白（MTCH2）是线粒体氧化磷酸化（OXPHOS）的抑制剂，其基因座与人类 BMI 的增加有关。在这里，我们证明肌肉组织中 MTCH2 缺失的小鼠可以防止饮食诱导的肥胖和高胰岛素血症，并且它们表现出更高的能量消耗。肌肉组织中 MTCH2 的缺失还会增加线粒体 OXPHOS 和质量，促使从糖酵解向氧化纤维转化，增加耐力运动能力，并增强心脏功能。此外，肌肉组织中 MTCH2 缺失的小鼠的代谢谱分析显示，它们对碳水化合物的利用有偏好，并且肌肉中的线粒体和糖酵解通量增加。因此，MTCH2 是肌肉生物学中的关键参与者，调节代谢和线粒体质量，以及影响全身能量稳态。
