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MICU1 Interacts with the D-Ring of the MCU Pore to Control Its Ca 2+ Flux and Sensitivity to Ru360

MICU1 Interacts with the D-Ring of the MCU Pore to Control Its Ca 2+ Flux and Sensitivity to Ru360

Melanie Paillard, György Csordás, Kai-Ting Huang, Peter Várnai, Suresh K Joseph, György Hajnóczky

Mol Cell. 2018 Nov 15;72(4):778-785.e3.

PMID: 30454562

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4249119	Ru360			Price

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