Document Type
Article
Publication Date
11-15-2018
Abstract
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.
Recommended Citation
Paillard, Melanie; Csordás, György; Huang, Kai-Ting; Várnai, Peter; Joseph, Suresh K.; and Hajnóczky, György, "MICU1 Interacts with the D-Ring of the MCU Pore to Control Its Ca2+ Flux and Sensitivity to Ru360" (2018). Department of Pathology, Anatomy, and Cell Biology Faculty Papers. Paper 290.
https://jdc.jefferson.edu/pacbfp/290
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
PubMed ID
30454562
Language
English
Comments
This article has been peer reviewed. It is the authors' final version prior to publication in Molecular Cell, Volume 72, Issue 4, November 2019, Pages 778-785.e3.
The published version is available at https://doi.org/10.1016/j.molcel.2018.09.008. Copyright © Paillard et al.