MICU1和MICU2在线粒体钙摄取中的功能作用。

Functional roles of MICU1 and MICU2 in mitochondrial Ca(2+) uptake.

作者信息

Matesanz-Isabel Jessica, Arias-del-Val Jessica, Alvarez-Illera Pilar, Fonteriz Rosalba I, Montero Mayte, Alvarez Javier

机构信息

Instituto de Biología y Genética Molecular (IBGM), Departamento de Bioquímica y Biología Molecular y Fisiología, Facultad de Medicina, Universidad de Valladolid and Consejo Superior de Investigaciones Científicas (CSIC), Ramón y Cajal, 7, E-47005 Valladolid, Spain.

出版信息

Biochim Biophys Acta. 2016 Jun;1858(6):1110-7. doi: 10.1016/j.bbamem.2016.02.022. Epub 2016 Feb 18.

DOI:10.1016/j.bbamem.2016.02.022

PMID:26903221

Abstract

MICU1 and MICU2 are the main regulators of the mitochondrial Ca(2+)-uniporter (MCU), but their precise functional role is still under debate. We show here that MICU2 behaves as a pure inhibitor of MCU at low cytosolic [Ca(2+)] ([Ca(2+)]c), though its effects decrease as [Ca(2+)]c is increased and disappear above 7 μM. Regarding MICU1, studying its effects is more difficult because knockdown of MICU1 leads also to loss of MICU2. However, while knockdown of MICU2 induces only a persistent increase in mitochondrial Ca(2+) uptake, knockdown of MICU1 also induces a peculiar use-dependent transient activation of MCU that cannot be attributed to the parallel loss of MICU2. Therefore, MICU1 is endowed with a specific inhibitory effect on MCU at low [Ca(2+)]c, separate and kinetically different from that of MICU2. On the other hand, we and others have shown previously that MICU1 activates MCU at [Ca(2+)]c above 2.5 μM. Thus, MICU1 has a double role in MCU regulation, inhibitory at low [Ca(2+)]c and activatory at high [Ca(2+)]c.

摘要

线粒体钙单向转运体（MCU）的主要调节因子是MICU1和MICU2，但其确切的功能作用仍存在争议。我们在此表明，在低胞质钙离子浓度（[Ca(2+)]c）下，MICU2表现为MCU的纯抑制剂，不过随着[Ca(2+)]c升高，其作用减弱，在7 μM以上时作用消失。关于MICU1，研究其作用更为困难，因为敲低MICU1也会导致MICU2缺失。然而，敲低MICU2仅导致线粒体钙摄取持续增加，而敲低MICU1还会诱导MCU出现一种特殊的使用依赖性瞬时激活，这不能归因于MICU2的平行缺失。因此，在低[Ca(2+)]c时，MICU1对MCU具有特定的抑制作用，这与MICU2的抑制作用不同，且在动力学上也有差异。另一方面，我们和其他人之前已经表明，在[Ca(2+)]c高于2.5 μM时，MICU1会激活MCU。因此，MICU1在MCU调节中具有双重作用，在低[Ca(2+)]c时起抑制作用，在高[Ca(2+)]c时起激活作用。