Colombini Marco
Department of Biology, University of Maryland, College Park, MD 20742, USA.
Biochim Biophys Acta. 2012 Jun;1818(6):1457-65. doi: 10.1016/j.bbamem.2011.12.026. Epub 2012 Jan 3.
VDAC channels exist in the mitochondrial outer membrane of all eukaryotic organisms. Of the different isoforms present in one organism, it seems that one of these is the canonical VDAC whose properties and 3D structure are highly conserved. The fundamental role of these channels is to control the flux of metabolites between the cytosol and mitochondrial spaces. Based on many functional studies, the fundamental structure of the pore wall consists of one α helix and 13 β strands tilted at a 46° angle. This results in a pore with an estimated internal diameter of 2.5nm. This structure has not yet been resolved. The published 3D structure consists of 19 β strands and is different from the functional structure that forms voltage-gated channels. The selectivity of the channel is exquisite, being able to select for ATP over molecules of the same size and charge. Voltage gating involves two separate gating processes. The mechanism involves the translocation of a positively charged portion of the wall of the channel to the membrane surface resulting in a reduction in pore diameter and volume and an inversion in ion selectivity. This mechanism is consistent with experiments probing changes in selectivity, voltage gating, kinetics and energetics. Other published mechanisms are in conflict with experimental results. This article is part of a Special Issue entitled: VDAC structure, function, and regulation of mitochondrial metabolism.
电压依赖性阴离子通道（VDAC）存在于所有真核生物的线粒体外膜中。在一种生物体内存在的不同亚型中，似乎有一种是典型的VDAC，其特性和三维结构高度保守。这些通道的基本作用是控制代谢物在细胞质和线粒体空间之间的通量。基于许多功能研究，孔壁的基本结构由一个α螺旋和13条以46°角倾斜的β链组成。这导致形成一个内径估计为2.5nm的孔。这种结构尚未得到解析。已发表的三维结构由19条β链组成，与形成电压门控通道的功能结构不同。该通道的选择性非常精细，能够在大小和电荷相同的分子中选择ATP。电压门控涉及两个独立的门控过程。其机制涉及通道壁带正电部分向膜表面的移位，导致孔径和体积减小以及离子选择性反转。该机制与探测选择性、电压门控、动力学和能量学变化的实验结果一致。其他已发表的机制与实验结果相冲突。本文是名为“VDAC的结构、功能及线粒体代谢调控”的特刊的一部分。
