Proper control of the mitochondrial Ca uniporter's pore (MCU) is required to allow Ca-dependent activation of oxidative metabolism and to avoid mitochondrial Ca overload and cell death. The MCU's gatekeeping and cooperative activation is mediated by the Ca-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.
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| http://dx.doi.org/10.1016/j.molcel.2018.09.008 | DOI Listing |
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