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 CitationPaillard, 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.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.