MICU1 Interacts with the D-Ring of the MCU Pore to Control Its Ca2+ Flux and Sensitivity to Ru360

被引：110

作者：

Paillard, Melanie ^{[1
]}

Csordas, Gyorgy ^{[1
]}

Huang, Kai-Ting ^{[1
]}

Varnai, Peter ^{[2
]}

Joseph, Suresh K. ^{[1
]}

Hajnoczky, Gyorgy ^{[1
]}

机构：

[1] Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, MitoCare Ctr, Philadelphia, PA 19107 USA

[2] Semmelweis Univ, Dept Physiol, H-1094 Budapest, Hungary

来源：

MOLECULAR CELL | 2018年 / 72卷 / 04期

关键词：

MITOCHONDRIAL CALCIUM UNIPORTER; BINDING; GATEKEEPER; SURVIVAL; SERVES;

D O I：

10.1016/j.molcel.2018.09.008

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Proper control of the mitochondrial Ca2+ uniporter's pore (MCU) is required to allow Ca2+-dependent activation of oxidative metabolism and to avoid mitochondrial Ca2+ overload and cell death. The MCU's gatekeeping and cooperative activation is mediated by the Ca2+-sensing MICU1 protein, which has been proposed to form dimeric complexes anchored to the EMRE scaffold of MCU. We unexpectedly find that MICU1 suppresses inhibition of MCU by ruthenium red/Ru360, which bind to MCU's DIME motif, the selectivity filter. This led us to recognize in MICU1's sequence a putative DIME interacting domain (DID), which is required for both gatekeeping and cooperative activation of MCU and for cell survival. Thus, we propose that MICU1 has to interact with the D-ring formed by the DIME domains in MCU to control the uniporter.

引用

页码：778 / +

页数：11

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