| First Author | Paillard M | Year | 2018 |
| Journal | Mol Cell | Volume | 72 |
| Issue | 4 | Pages | 778-785.e3 |
| PubMed ID | 30454562 | Mgi Jnum | J:269007 |
| Mgi Id | MGI:6270051 | Doi | 10.1016/j.molcel.2018.09.008 |
| Citation | Paillard M, et al. (2018) MICU1 Interacts with the D-Ring of the MCU Pore to Control Its Ca(2+) Flux and Sensitivity to Ru360. Mol Cell 72(4):778-785.e3 |
| abstractText | Proper control of the mitochondrial Ca(2+) uniporter's pore (MCU) is required to allow Ca(2+)-dependent activation of oxidative metabolism and to avoid mitochondrial Ca(2+) overload and cell death. The MCU's gatekeeping and cooperative activation is mediated by the Ca(2+)-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. |
