O'Rourke Brian
Institute of Molecular Cardiobiology, Division of Cardiology, Department of Medicine, The Johns Hopkins University, Baltimore, Maryland 21205, USA.
Annu Rev Physiol. 2007;69:19-49. doi: 10.1146/annurev.physiol.69.031905.163804.
In work spanning more than a century, mitochondria have been recognized for their multifunctional roles in metabolism, energy transduction, ion transport, inheritance, signaling, and cell death. Foremost among these tasks is the continuous production of ATP through oxidative phosphorylation, which requires a large electrochemical driving force for protons across the mitochondrial inner membrane. This process requires a membrane with relatively low permeability to ions to minimize energy dissipation. However, a wealth of evidence now indicates that both selective and nonselective ion channels are present in the mitochondrial inner membrane, along with several known channels on the outer membrane. Some of these channels are active under physiological conditions, and others may be activated under pathophysiological conditions to act as the major determinants of cell life and death. This review summarizes research on mitochondrial ion channels and efforts to identify their molecular correlates. Except in a few cases, our understanding of the structure of mitochondrial ion channels is limited, indicating the need for focused discovery in this area.
在跨越一个多世纪的研究工作中,线粒体因其在代谢、能量转导、离子转运、遗传、信号传导和细胞死亡等方面的多功能作用而被人们所认识。这些任务中最重要的是通过氧化磷酸化持续产生ATP,这需要线粒体内膜上存在较大的质子电化学驱动力。这个过程需要一种对离子通透性相对较低的膜,以尽量减少能量耗散。然而,现在大量证据表明,线粒体内膜中存在选择性和非选择性离子通道,外膜上也有几种已知的通道。其中一些通道在生理条件下是活跃的,而其他一些通道可能在病理生理条件下被激活,从而成为细胞生死的主要决定因素。这篇综述总结了关于线粒体离子通道的研究以及识别其分子关联的努力。除了少数情况外,我们对线粒体离子通道结构的理解有限,这表明在该领域需要有针对性的探索。