Department of Cell Biology, University of Geneva, Switzerland.
Cell Calcium. 2010 Jan;47(1):11-8. doi: 10.1016/j.ceca.2009.10.005. Epub 2009 Nov 26.
Mitochondria play a major role in cellular calcium homeostasis. Despite decades of studies, the molecules that mediate and regulate the transport of calcium ions in and out of the mitochondrial matrix remain unknown. Here, we investigate whether SLP-2, an inner membrane mitochondrial protein of unknown function, modulates the activity of mitochondrial Ca(2+) transporters. In HeLa cells depleted of SLP-2, the amplitude and duration of mitochondrial Ca(2+) elevations evoked by agonists were decreased compared to control cells. SLP-2 depletion increased the rates of calcium extrusion from mitochondria. This effect disappeared upon Na(+) removal or addition of CGP-37157, an inhibitor of the mitochondrial Na(+)/Ca(2+) exchanger, and persisted in permeabilized cells exposed to a fixed cytosolic Na(+) and Ca(2+) concentration. The rates of mitochondrial Ca(2+) extrusion were prolonged in SLP-2 over-expressing cells, independently of the amplitude of mitochondrial Ca(2+) elevations. The amplitude of cytosolic Ca(2+) elevations was increased by SLP-2 depletion and decreased by SLP-2 over-expression. These data show that SLP-2 modulates mitochondrial calcium extrusion, thereby altering the ability of mitochondria to buffer Ca(2+) and to shape cytosolic Ca(2+) signals.
线粒体在细胞钙离子稳态中起着重要作用。尽管已经进行了数十年的研究，但介导和调节钙离子进出线粒体基质的分子仍然未知。在这里，我们研究了未知功能的内膜线粒体蛋白 SLP-2 是否调节线粒体 Ca(2+)转运体的活性。在 SLP-2 耗尽的 HeLa 细胞中，与对照细胞相比，激动剂引起的线粒体 Ca(2+)升高的幅度和持续时间降低。SLP-2 耗尽增加了线粒体钙外排的速率。这种效应在去除 Na+(或添加线粒体 Na(+)/Ca(2+)交换器抑制剂 CGP-37157)后消失，并在暴露于固定胞浆 Na(+)和 Ca(2+)浓度的通透细胞中持续存在。在 SLP-2 过表达细胞中，线粒体 Ca(2+)外排的速率延长，而与线粒体 Ca(2+)升高的幅度无关。SLP-2 耗尽会增加细胞浆 Ca(2+)升高的幅度，而过表达则会降低其幅度。这些数据表明，SLP-2 调节线粒体钙外排，从而改变线粒体缓冲 Ca(2+)和塑造细胞浆 Ca(2+)信号的能力。
