Department of Cell Physiology and Metabolism, University of Geneva, University Medical Center, Switzerland.
Cell Metab. 2011 May 4;13(5):601-11. doi: 10.1016/j.cmet.2011.03.015.
Mitochondrial Ca(2+) signals have been proposed to accelerate oxidative metabolism and ATP production to match Ca(2+)-activated energy-consuming processes. Efforts to understand the signaling role of mitochondrial Ca(2+) have been hampered by the inability to manipulate matrix Ca(2+) without directly altering cytosolic Ca(2+). We were able to selectively buffer mitochondrial Ca(2+) rises by targeting the Ca(2+)-binding protein S100G to the matrix. We find that matrix Ca(2+) controls signal-dependent NAD(P)H formation, respiration, and ATP changes in intact cells. Furthermore, we demonstrate that matrix Ca(2+) increases are necessary for the amplification of sustained glucose-dependent insulin secretion in β cells. Through the regulation of NAD(P)H in adrenal glomerulosa cells, matrix Ca(2+) also acts as a positive signal in reductive biosynthesis, which stimulates aldosterone secretion. Our dissection of cytosolic and mitochondrial Ca(2+) signals reveals the physiological importance of matrix Ca(2+) in energy metabolism required for signal-dependent hormone secretion.
线粒体 Ca(2+) 信号被认为可以加速氧化代谢和 ATP 生成，以匹配 Ca(2+) 激活的耗能过程。由于无法在不直接改变胞质 Ca(2+)的情况下操纵基质 Ca(2+)，因此理解线粒体 Ca(2+) 的信号作用一直受到阻碍。我们通过将 Ca(2+) 结合蛋白 S100G 靶向基质，成功地选择性缓冲线粒体 Ca(2+) 的上升。我们发现基质 Ca(2+) 控制着完整细胞中信号依赖性 NAD(P)H 的形成、呼吸和 ATP 变化。此外，我们证明基质 Ca(2+) 的增加对于 β 细胞中持续葡萄糖依赖性胰岛素分泌的放大是必需的。通过调节肾上腺球状带细胞中的 NAD(P)H，基质 Ca(2+) 也作为还原生物合成中的正信号，刺激醛固酮的分泌。我们对胞质和线粒体 Ca(2+) 信号的剖析揭示了基质 Ca(2+) 在信号依赖性激素分泌所需的能量代谢中的生理重要性。
