Rearrangement of MICU1 multimers for activation of MCU is solely controlled by cytosolic Ca(2.).
Rearrangement of MICU1 multimers for activation of MCU is solely controlled by cytosolic Ca(2.).
复制标题
MICU1多聚体以激活MCU的重排仅由胞质CA控制（2。）。
DOI：
10.1038/srep15602
复制
发表时间：
2015-10-22
影响因子：
4.6
通讯作者：
Graier WF
中科院分区：
文献类型：
--
作者：
Waldeck-Weiermair M;Malli R;Parichatikanond W;Gottschalk B;Madreiter-Sokolowski CT;Klec C;Rost R;Graier WF
Mitochondrial Ca2+ uptake is a vital process that controls distinct cell and organelle functions. Mitochondrial calcium uptake 1 (MICU1) was identified as key regulator of the mitochondrial Ca2+ uniporter (MCU) that together with the essential MCU regulator (EMRE) forms the mitochondrial Ca2+ channel. However, mechanisms by which MICU1 controls MCU/EMRE activity to tune mitochondrial Ca2+ signals remain ambiguous. Here we established a live-cell FRET approach and demonstrate that elevations of cytosolic Ca2+ rearranges MICU1 multimers with an EC50 of 4.4 μM, resulting in activation of mitochondrial Ca2+ uptake. MICU1 rearrangement essentially requires the EF-hand motifs and strictly correlates with the shape of cytosolic Ca2+ rises. We further show that rearrangements of MICU1 multimers were independent of matrix Ca2+ concentration, mitochondrial membrane potential, and expression levels of MCU and EMRE. Our experiments provide novel details about how MCU/EMRE is regulated by MICU1 and an original approach to investigate MCU/EMRE activation in intact cells.
