ULB Center for Diabetes Research, University of Brussels (ULB), 1050 Brussels, Belgium.
Laboratory of Biochemistry and Cell Biology (URBC), NARILIS (Namur Research Institute for Life Sciences), University of Namur (UNamur), 5000 Namur, Belgium.
Cells. 2019 Jul 30;8(8):795. doi: 10.3390/cells8080795.
Mitochondrial uncoupling can be defined as a dissociation between mitochondrial membrane potential generation and its use for mitochondria-dependent ATP synthesis. Although this process was originally considered a mitochondrial dysfunction, the identification of UCP-1 as an endogenous physiological uncoupling protein suggests that the process could be involved in many other biological processes. In this review, we first compare the mitochondrial uncoupling agents available in term of mechanistic and non-specific effects. Proteins regulating mitochondrial uncoupling, as well as chemical compounds with uncoupling properties are discussed. Second, we summarize the most recent findings linking mitochondrial uncoupling and other cellular or biological processes, such as bulk and specific autophagy, reactive oxygen species production, protein secretion, cell death, physical exercise, metabolic adaptations in adipose tissue, and cell signaling. Finally, we show how mitochondrial uncoupling could be used to treat several human diseases, such as obesity, cardiovascular diseases, or neurological disorders.
线粒体解偶联可以定义为线粒体膜电位产生与其用于依赖线粒体的 ATP 合成之间的分离。虽然这个过程最初被认为是一种线粒体功能障碍，但 UCP-1 作为内源性生理解偶联蛋白的鉴定表明，该过程可能涉及许多其他生物学过程。在这篇综述中，我们首先比较了在机制和非特异性效应方面可用的线粒体解偶联剂。讨论了调节线粒体解偶联的蛋白质以及具有解偶联特性的化学化合物。其次，我们总结了最近将线粒体解偶联与其他细胞或生物学过程联系起来的发现，例如自噬、活性氧物质的产生、蛋白质分泌、细胞死亡、体育锻炼、脂肪组织的代谢适应以及细胞信号转导。最后，我们展示了如何使用线粒体解偶联来治疗几种人类疾病，如肥胖症、心血管疾病或神经紊乱。
