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The mitochondrial calcium uniporter is a highly selective ion channel

机译：线粒体钙单向转运蛋白是高度选择性的离子通道

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摘要

During intracellular Ca~(2+) signalling mitochondria accumulate significant amounts of Ca~(2+) from the cytosol. Mitochondrial Ca~(2+) uptake controls the rate of energy production, shapes the amplitude and spatio-temporal patterns of intracellular Ca~(2+) signals, and is instrumental to cell death. This Ca~(2+) uptake is undertaken by the mitochondrial Ca~(2+) uniporter (MCU) located in the organdie's inner membrane. The uniporter passes Ca~(2+) down the electrochemical gradient maintained across this membrane without direct coupling to ATP hydrolysis or transport of other ions. 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 channel. By patch-clamping the inner mitochondrial membrane, we identified a previously unknown Ca~(2+)-selective ion channel sensitive to inhibitors of mitochondrial Ca~(2+) uptake. Our data indicate that this unique channel binds Ca~(2+) with extremely high affinity (dissociation constant ≤2 nM), enabling high Ca~(2+) selectivity despite relatively low cytoplasmic Ca~(2+) concentrations. The channel is inwardly rectifying, making it especially effective for Ca~(2+) uptake into energized mitochondria. Thus, we conclude that the properties of the current mediated by this novel channel are those of the MCU.
机译：在细胞内Ca〜（2+）信号线粒体从细胞质中积累了大量的Ca〜（2+）。线粒体Ca〜（2+）的摄取控制能量产生的速率，影响细胞内Ca〜（2+）信号的振幅和时空模式，并有助于细胞死亡。 Ca〜（2+）的吸收是由位于细胞器内膜的线粒体Ca〜（2+）单向转运蛋白（MCU）承担的。单向体使Ca〜（2+）沿着保持在该膜上的电化学梯度向下传递，而没有与ATP水解或其他离子的运输直接耦合。运营商的特点是周转率通常比离子通道低1,000倍，并且到目前为止，还不清楚MCU是运营商还是渠道。通过膜片钳内线粒体膜，我们确定了以前未知的Ca〜（2 +）-选择性离子通道对线粒体Ca〜（2+）吸收的抑制剂敏感。我们的数据表明，该独特通道以极高的亲和力（解离常数≤2nM）结合Ca〜（2+），尽管细胞质Ca〜（2+）浓度相对较低，但仍具有很高的Ca〜（2+）选择性。该通道向内整流，使其特别有效地吸收Ca〜（2+）进入线粒体。因此，我们得出的结论是，由这种新颖的通道介导的电流属性是MCU的那些属性。

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  • 来源
    《Nature》 |2004年第6972期|p.360-364|共5页
  • 作者

    Yuriy Kirichok; Grlgory Krapivinsky; David E. Clapham;

  • 作者单位

    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;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 自然科学总论;
  • 关键词

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