生物谷報道： 線粒體對鈣的吸收是首次于1961年觀察到的,，被認為是通過一個Uniporter進行的。一個Uniporter是一種膜蛋白,，調節(jié)目標離子的運輸,，而又不將這種運輸與任何其他分子或離子的運輸聯(lián)系起來。鈣的Uniporter在線粒體中扮演著一個非常重要的角色,，使Ca2+具有高滲透性,，而使K+無法滲透，即便在胞質中Ca2+水平很低時也是如此,。但Uniporter卻難以純化或克隆,，它是一種載體還是一種通道也一直不清楚。現(xiàn)在,，Kirichok等人識別出一種新穎的鈣通道,，它所具有的性質與人們長期尋找的鈣的Uniporter的性質一致,。穿過線粒體內膜的電流是在整個線粒質（沒有外層膜的線粒體）中測定的。這一假定的鈣Uniporter在非常低的負電勢下打開,，這使得Ca2+可有效運輸進激發(fā)的線粒體中,。
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. ([email protected]).
During intracellular Ca2+ signalling mitochondria accumulate significant amounts of Ca2+ from the cytosol1, 2. Mitochondrial Ca2+ uptake controls the rate of energy production1, 3, 4, shapes the amplitude and spatio-temporal patterns of intracellular Ca2+ signals1, 5-8, and is instrumental to cell death9, 10. This Ca2+ uptake is undertaken by the mitochondrial Ca2+ uniporter (MCU) located in the organelle's inner membrane11, 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.
