Marchi Saverio, Pinton Paolo
Department of Morphology; Surgery and Experimental Medicine; Section of General Pathology; Interdisciplinary Center for the Study of Inflammation (ICSI); Laboratory for Technologies of Advanced Therapies (LTTA); University of Ferrara; Ferrara, Italy.
Commun Integr Biol. 2013 May 1;6(3):e23818. doi: 10.4161/cib.23818. Epub 2013 May 13.
Mitochondria receive calcium (Ca(2+)) signals from endoplasmic reticulum (ER) and decode them into pro-apoptotic inputs, which lead to cell death. Therefore, mitochondrial Ca(2+) overload is considered a fundamental trigger of the apoptotic process, and several oncogenes and tumor suppressors modify the activity of protein involved in Ca(2+) homeostasis to control apoptosis. The identification of the channel responsible for mitochondrial Ca(2+) entry, the Mitochondrial Ca(2+)Uniporter (MCU), together with its regulatory components, MICU1 and MCUR1, provides new molecular tools to investigate this process. Recent data have also shown that miR-25 decreases mitochondrial Ca(2+) uptake through selective MCU downregulation, conferring resistance to apoptotic challenges. MCU appears to be downregulated in human colon cancer samples, and accordingly, miR-25 is aberrantly expressed, indicating the importance of mitochondrial Ca(2+) regulation in cancer cell survival.
线粒体接收来自内质网（ER）的钙（Ca(2+)）信号，并将其解码为促凋亡输入信号，从而导致细胞死亡。因此，线粒体Ca(2+)过载被认为是凋亡过程的一个基本触发因素，并且一些癌基因和肿瘤抑制因子会改变参与Ca(2+)稳态的蛋白质活性以控制细胞凋亡。负责线粒体Ca(2+)内流的通道——线粒体钙单向转运体（MCU）及其调节成分MICU1和MCUR1的鉴定，为研究这一过程提供了新的分子工具。最近的数据还表明，miR-25通过选择性下调MCU来减少线粒体Ca(2+)摄取，赋予细胞对凋亡挑战的抗性。MCU在人类结肠癌样本中似乎被下调，相应地，miR-25异常表达，这表明线粒体Ca(2+)调节在癌细胞存活中具有重要意义。
