线粒体钙uniport通道被发现

生物谷

生物谷报道：线粒体对钙的吸收是首次于1961年观察到的，被认为是通过一个Uniporter进行的。一个Uniporter是一种膜蛋白，调节目标离子的运输，而又不将这种运输与任何其他分子或离子的运输联系起来。钙的Uniporter在线粒体中扮演着一个非常重要的角色，使Ca2+具有高渗透性，而使K+无法渗透，即便在胞质中Ca2+水平很低时也是如此。但Uniporter却难以纯化或克隆，它是一种载体还是一种通道也一直不清楚。现在，Kirichok等人识别出一种新颖的钙通道，它所具有的性质与人们长期寻找的钙的Uniporter的性质一致。穿过线粒体内膜的电流是在整个线粒质（没有外层膜的线粒体）中测定的。这一假定的钙Uniporter在非常低的负电势下打开，这使得Ca2+可有效运输进激发的线粒体中。

Nature 427, 360 - 364 (22 January 2004); doi:10.1038/nature02246

The mitochondrial calcium uniporter is a highly selective ion channel

YURIY KIRICHOK, GRIGORY KRAPIVINSKY & DAVID E. CLAPHAM

Howard Hughes Medical Institute, Department of Cardiovascular Research, Children's Hospital, and Department of Neurobiology, Harvard Medical School, 320 Longwood Avenue, Boston, Massachusetts 02115, USA

Correspondence and requests for materials should be addressed to D.E.C. (dclapham@enders.tch.harvard.edu).

During intracellular Ca²⁺ signalling mitochondria accumulate significant amounts of Ca²⁺ from the cytosol^{1, 2}. Mitochondrial Ca²⁺ uptake controls the rate of energy production^{1, 3, 4}, shapes the amplitude and spatio-temporal patterns of intracellular Ca²⁺ signals^{1, 5-8}, and is instrumental to cell death^{9, 10}. This Ca²⁺ uptake is undertaken by the mitochondrial Ca²⁺ uniporter (MCU) located in the organelle's inner membrane^{11, 12}. The uniporter passes Ca²⁺ down the electRochemical gradient maintained across this membrane without direct coupling to ATP hydrolysis or transport of other ions¹¹. Carriers are characterized by turnover numbers that are typically 1,000-fold lower than ion channels, and until now it has been unclear whether the MCU is a carrier or a channel¹³. By patch-clamping the inner mitochondrial membrane, we identified a previously unknown Ca²⁺-selective ion channel sensitive to inhibitors of mitochondrial Ca²⁺ uptake. Our data indicate that this unique channel binds Ca²⁺ with extremely high affinity (dissociation constant 2 nM), enabling high Ca²⁺ selectivity despite relatively low cytoplasmic Ca²⁺ concentrations. The channel is inwardly rectifying, making it especially effective for Ca²⁺ uptake into energized mitochondria. Thus, we conclude that the properties of the current mediated by this novel channel are those of the MCU.