Mnatsakanyan Nelli, Beutner Gisela, Porter George A, Alavian Kambiz N, Jonas Elizabeth A
Department Internal Medicine, Section of Endocrinology, Yale University, New Haven, CT, USA.
Department of Pediatrics (Cardiology), University of Rochester Medical Center, Rochester, NY, USA.
J Bioenerg Biomembr. 2017 Feb;49(1):13-25. doi: 10.1007/s10863-016-9652-1. Epub 2016 Feb 11.
Neurons experience high metabolic demand during such processes as synaptic vesicle recycling, membrane potential maintenance and Ca exchange/extrusion. The energy needs of these events are met in large part by mitochondrial production of ATP through the process of oxidative phosphorylation. The job of ATP production by the mitochondria is performed by the FF ATP synthase, a multi-protein enzyme that contains a membrane-inserted portion, an extra-membranous enzymatic portion and an extensive regulatory complex. Although required for ATP production by mitochondria, recent findings have confirmed that the membrane-confined portion of the c-subunit of the ATP synthase also houses a large conductance uncoupling channel, the mitochondrial permeability transition pore (mPTP), the persistent opening of which produces osmotic dysregulation of the inner mitochondrial membrane, uncoupling of oxidative phosphorylation and cell death. Recent advances in understanding the molecular components of mPTP and its regulatory mechanisms have determined that decreased uncoupling occurs in states of enhanced mitochondrial efficiency; relative closure of mPTP therefore contributes to cellular functions as diverse as cardiac development and synaptic efficacy.
在诸如突触小泡循环、膜电位维持和钙交换/外排等过程中，神经元经历着高代谢需求。这些活动的能量需求在很大程度上通过线粒体通过氧化磷酸化过程产生ATP来满足。线粒体产生ATP的工作由F₀F₁ATP合酶完成，这是一种多蛋白酶，包含一个插入膜的部分、一个膜外酶部分和一个广泛的调节复合体。尽管线粒体产生ATP需要它，但最近的研究结果证实，ATP合酶c亚基的膜封闭部分还容纳一个大电导解偶联通道，即线粒体通透性转换孔（mPTP），其持续开放会导致线粒体内膜的渗透调节异常、氧化磷酸化解偶联和细胞死亡。在理解mPTP的分子成分及其调节机制方面的最新进展已经确定，在线粒体效率增强的状态下解偶联减少；因此，mPTP的相对关闭有助于多种细胞功能，如心脏发育和突触效能。
