Pecqueur Claire, Bui Thi, Gelly Chantal, Hauchard Julie, Barbot Céline, Bouillaud Frederic, Ricquier Daniel, Miroux Bruno, Thompson Craig B
Université Paris Descartes, CNRS-UPR9078, Faculté de Médecine site Necker, 156 rue de vaugirard, 75730 Paris Cedex 15, France.
FASEB J. 2008 Jan;22(1):9-18. doi: 10.1096/fj.07-8945com. Epub 2007 Sep 13.
Uncoupling protein-2 (UCP2) belongs to the mitochondrial carrier family and has been thought to be involved in suppressing mitochondrial ROS production through uncoupling mitochondrial respiration from ATP synthesis. However, we show here that loss of function of UCP2 does not result in a significant increase in ROS production or an increased propensity for cells to undergo senescence in culture. Instead, Ucp2-/- cells display enhanced proliferation associated with a metabolic switch from fatty acid oxidation to glucose metabolism. This metabolic switch requires the unrestricted availability of glucose, and Ucp2-/- cells more readily activate autophagy than wild-type cells when deprived of glucose. Altogether, these results suggest that UCP2 promotes mitochondrial fatty acid oxidation while limiting mitochondrial catabolism of pyruvate. The persistence of fatty acid catabolism in Ucp2+/+ cells during a proliferative response correlates with reduced cell proliferation and enhances resistance to glucose starvation-induced autophagy.
解偶联蛋白2（UCP2）属于线粒体载体家族，一直被认为通过使线粒体呼吸与ATP合成解偶联来参与抑制线粒体活性氧的产生。然而，我们在此表明，UCP2功能丧失不会导致活性氧产生显著增加，也不会使培养的细胞衰老倾向增加。相反，Ucp2-/-细胞显示出增殖增强，这与从脂肪酸氧化到葡萄糖代谢的代谢转换有关。这种代谢转换需要葡萄糖的不受限制的可用性，并且当缺乏葡萄糖时，Ucp2-/-细胞比野生型细胞更容易激活自噬。总之，这些结果表明UCP2促进线粒体脂肪酸氧化，同时限制丙酮酸的线粒体分解代谢。在增殖反应期间Ucp2+/+细胞中脂肪酸分解代谢的持续存在与细胞增殖减少相关，并增强对葡萄糖饥饿诱导的自噬的抗性。
