It was recently asserted that the voltage-dependent anion channel (VDAC) serves as a global regulator, or governor, of mitochondrial function (Lemasters and Holmuhamedov, Biochim Biophys Acta 1762:181-190, 2006). Indeed, VDAC, positioned on the interface between mitochondria and the cytosol (Colombini, Mol Cell Biochem 256:107-115, 2004), is at the control point of mitochondria life and death. This large channel plays the role of a "switch" that defines in which direction mitochondria will go: to normal respiration or to suppression of mitochondria metabolism that leads to apoptosis and cell death. As the most abundant protein in the mitochondrial outer membrane (MOM), VDAC is known to be responsible for ATP/ADP exchange and for the fluxes of other metabolites across MOM. It controls them by switching between the open and "closed" states that are virtually impermeable to ATP and ADP. This control has dual importance: in maintaining normal mitochondria respiration and in triggering apoptosis when cytochrome c and other apoptogenic factors are released from the intermembrane space into the cytosol. Emerging evidence indicates that VDAC closure promotes apoptotic signals without direct involvement of VDAC in the permeability transition pore or hypothetical Bax-containing cytochrome c permeable pores. VDAC gating has been studied extensively for the last 30 years on reconstituted VDAC channels. In this review we focus exclusively on physiologically relevant regulators of VDAC gating such as endogenous cytosolic proteins and mitochondrial lipids. Closure of VDAC induced by such dissimilar cytosolic proteins as pro-apoptotic tBid and dimeric tubulin is compared to show that the involved mechanisms are rather distinct. While tBid mostly modulates VDAC voltage gating, tubulin blocks the channel with the efficiency of blockage controlled by voltage. We also discuss how characteristic mitochondrial lipids, phospatidylethanolamine and cardiolipin, could regulate VDAC gating. Overall, we demonstrate that VDAC gating is not just an observation made under artificial conditions of channel reconstitution but is a major mechanism of MOM permeability control.

中文翻译：

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VDAC 调节：细胞质蛋白和线粒体脂质的作用。

最近有人断言，电压依赖性阴离子通道 (VDAC) 是线粒体功能的全局调节器或调控器（Lemasters 和 Holmuhamedov，Biochim Biophys Acta 1762：181-190，2006）。事实上，VDAC 位于线粒体和细胞质之间的界面上（Colombini, Mol Cell Biochem 256:107-115, 2004），处于线粒体生死的控制点。这个大通道起着“开关”的作用，它定义了线粒体将走向的方向：正常呼吸或抑制导致细胞凋亡和细胞死亡的线粒体代谢。作为线粒体外膜 (MOM) 中最丰富的蛋白质，已知 VDAC 负责 ATP/ADP 交换和其他代谢物跨 MOM 的通量。它通过在打开和“ 比较由诸如促凋亡 tBid 和二聚微管蛋白等不同的胞质蛋白诱导的 VDAC 关闭，以表明所涉及的机制相当不同。虽然 tBid 主要调节 VDAC 电压门控，但微管蛋白通过电压控制阻断效率来阻断通道。我们还讨论了线粒体脂质、磷脂酰乙醇胺和心磷脂如何调节 VDAC 门控。总的来说，我们证明 VDAC 门控不仅仅是在通道重建的人工条件下进行的观察，而且是 MOM 渗透率控制的主要机制。磷脂酰乙醇胺和心磷脂，可以调节 VDAC 门控。总的来说，我们证明了 VDAC 门控不仅仅是在通道重建的人工条件下进行的观察，而且是 MOM 渗透率控制的主要机制。磷脂酰乙醇胺和心磷脂，可以调节 VDAC 门控。总的来说，我们证明了 VDAC 门控不仅仅是在通道重建的人工条件下进行的观察，而且是 MOM 渗透率控制的主要机制。