Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University Graz, Austria.
Cell Calcium. 2010 May;47(5):433-40. doi: 10.1016/j.ceca.2010.03.004. Epub 2010 Apr 18.
The transmission of Ca(2+) signals to mitochondria is an important phenomenon in cell signaling. We have recently reported that the novel uncoupling proteins UCP2 and UCP3 (UCP2/3) are fundamental for mitochondrial Ca(2+) uniport (MCU). In the present study we investigate the contribution of UCP2/3 to mitochondrial accumulation of Ca(2+) either exclusively released from the ER or entering the cell via the store-operated Ca(2+) entry (SOCE) pathway. Using siRNA we demonstrate that constitutively expressed UCP2/3 are essentially involved in mitochondrial sequestration of intracellularly released Ca(2+) but not of that entering the cells via SOCE. However, overexpression of UCP2/3 yielded elevated mitochondrial Ca(2+) uptake from both sources, though it was more pronounced in case of entering Ca(2+), indicating that the expression levels of UCP2/3 are crucial for the capacity of mitochondria to sequester entering Ca(2+). Our data point to distinct UCP2/3-dependent and UCP2/3-independent modes of mitochondrial Ca(2+) sequestration, which may meet the various demands necessary for an adequate organelle Ca(2+) loading from different Ca(2+) sources in intact cells.
钙信号向线粒体的传递是细胞信号转导中的一个重要现象。我们最近的研究报告表明，新型解偶联蛋白 UCP2 和 UCP3（UCP2/3）是线粒体钙单向转运体（MCU）的基础。在本研究中，我们研究了 UCP2/3 对 ER 中单独释放或通过钙库操纵性钙内流（SOCE）途径进入细胞的 Ca2+ 进入线粒体的积累的贡献。通过 siRNA，我们证明组成型表达的 UCP2/3 主要参与细胞内释放的 Ca2+的线粒体摄取，但不参与通过 SOCE 进入细胞的 Ca2+摄取。然而，UCP2/3 的过表达导致两种来源的线粒体摄取 Ca2+增加，尽管进入细胞的 Ca2+增加更为明显，这表明 UCP2/3 的表达水平对于线粒体摄取进入的 Ca2+的能力至关重要。我们的数据表明存在依赖于 UCP2/3 和不依赖于 UCP2/3 的线粒体摄取 Ca2+的两种模式，这可能满足完整细胞中从不同 Ca2+源对细胞器进行适当 Ca2+加载的各种需求。
