MICU1 encodes a mitochondrial EF hand protein required for Ca2+ uptake
Fabiana Perocchi,Vishal M. Gohil,Hany S. Girgis,X. Robert Bao,Janet E. McCombs,Amy E. Palmer& Vamsi K. Mootha
Mitochondrial calcium uptake has a central role in cell physiology by stimulating ATP production, shaping cytosolic calcium transients and regulating cell death. The biophysical properties of mitochondrial calcium uptake have been studied in detail, but the underlying proteins remain elusive. Here we use an integrative strategy to predict human genes involved in mitochondrial calcium entry based on clues from comparative physiology, evolutionary genomics and organelle proteomics. RNA interference against 13 top candidates highlighted one gene, CBARA1, that we call hereafter mitochondrial calcium uptake 1 (MICU1). Silencing MICU1 does not disrupt mitochondrial respiration or membrane potential but abolishes mitochondrial calcium entry in intact and permeabilized cells, and attenuates the metabolic coupling between cytosolic calcium transients and activation of matrix dehydrogenases. MICU1 is associated with the mitochondrial inner membrane and has two canonical EF hands that are essential for its activity, indicating a role in calcium sensing. MICU1 represents the founding member of a set of proteins required for high-capacity mitochondrial calcium uptake. Its discovery may lead to the complete molecular characterization of mitochondrial calcium uptake pathways, and offers genetic strategies for understanding their contribution to normal physiology and disease.
Nature：调控线粒体钙吸收的蛋白MICU1
发布时间：2010-09-17 00:00 文章来源： 作者：
线粒体对钙的吸收是细胞功能很多方面的关键，其不平衡会触发细胞死亡。尽管如此，过去人们对调控线粒体对钙的吸收和缓冲的蛋白一个也不知道。现在，一种这样的蛋白（被命名为“线粒体钙吸收-1”或MICU1）已被识别出来。
MICU1局限于线粒体上，是钙吸收所专门需要的。MICU1 基因的破坏中断线粒体代谢与钙信号作用之间的代谢耦合。这项工作应能有助于对线粒体钙吸收机制及其在正常生理和疾病中所起作用进行分子定性。
Nature doi:10.1038/nature09358
MICU1 encodes a mitochondrial EF hand protein required for Ca2+ uptake
Fabiana Perocchi,Vishal M. Gohil,Hany S. Girgis,X. Robert Bao,Janet E. McCombs,Amy E. Palmer& Vamsi K. Mootha
Mitochondrial calcium uptake has a central role in cell physiology by stimulating ATP production, shaping cytosolic calcium transients and regulating cell death. The biophysical properties of mitochondrial calcium uptake have been studied in detail, but the underlying proteins remain elusive. Here we use an integrative strategy to predict human genes involved in mitochondrial calcium entry based on clues from comparative physiology, evolutionary genomics and organelle proteomics. RNA interference against 13 top candidates highlighted one gene, CBARA1, that we call hereafter mitochondrial calcium uptake 1 (MICU1). Silencing MICU1 does not disrupt mitochondrial respiration or membrane potential but abolishes mitochondrial calcium entry in intact and permeabilized cells, and attenuates the metabolic coupling between cytosolic calcium transients and activation of matrix dehydrogenases. MICU1 is associated with the mitochondrial inner membrane and has two canonical EF hands that are essential for its activity, indicating a role in calcium sensing. MICU1 represents the founding member of a set of proteins required for high-capacity mitochondrial calcium uptake. Its discovery may lead to the complete molecular characterization of mitochondrial calcium uptake pathways, and offers genetic strategies for understanding their contribution to normal physiology and disease.