线粒体钙离子转运
中文名称
通路描述
二价钙离子（Ca2+）从细胞质转运至线粒体基质，并从中转回细胞质（综述 Santo-Domingo 等 2010, De Stefani 等 2016）。在基质中，Ca2+ 结合并变构调节丙酮酸脱氢酶、异柠檬酸脱氢酶、α-酮戊二酸脱氢酶以及可能还有其他酶（Rizzuto 等 2012）。基质中的钙离子也被观察到调节 caspase 辅因子释放以及邻近膜上的钙离子通量。进入线粒体的途径涉及外膜中的 VDAC1、VDAC2 和 VDAC3，以及内膜中的线粒体钙 uniporter（MCU）复合物。VDAC 在开放构象下是阴离子通道。但在封闭构象下，它们将 Ca2+ 从细胞质转运至膜间空间。当细胞质和膜间空间的钙离子浓度较高时，MCU 复合物打开，利用膜电势作为驱动力将 Ca2+ 从膜间空间转运至线粒体基质（综述 Drago 等 2011, Marchi 等 2014, De Stefani 等 2015）。基质中 Ca2+ 向膜间空间的外排由位于内膜中的 Na+/Ca2+ 抗porter SLC8B1（NCLX）催化。LETM1 也被观察到通过作为 H+/Ca2+ 抗porter 将钙离子从基质转运至膜间空间，尽管在 LETM1 敲低中发现了部分矛盾的结果。膜间空间的钙离子可能通过 Na+/Ca2+ 抗porter SLC8A3（NCX3）转运至细胞质，但 SLC8A3 的线粒体定位存在争议，且 SLC8A3 在组织中的分布有限。
英文描述
Mitochondrial calcium ion transport Divalent calcium ions (Ca2+) are transported from the cytosol into the mitochondrial matrix and back out of the matrix into the cytosol (reviewed in Santo-Domingo et al. 2010, De Stefani et al. 2016). In the matrix, Ca2+ binds and allosterically regulates pyruvate dehydrogenase, isocitrate dehydrogenase, 2-oxoglutarate dehydrogenase, and possibly other enzymes (Rizzuto et al. 2012). Matrix calcium is also observed to regulate release of caspase cofactors and calcium flux through channels on neighboring membranes, The pathway into the mitochondrion involves VDAC1, VDAC2, and VDAC3 in the outer membrane and the mitochondrial calcium uniporter (MCU) complex in the inner membrane. VDACs in the open conformation are anion channels. However in the closed conformation they transport Ca2+ from the cytosol to the intermembrane space. When calcium concentrations in the cytosol and intermembrane space are high, the MCU complex opens and transports Ca2+ from the intermembrane space to the mitochondrial matrix using the driving force of the membrane potential (reviewed in Drago et al. 2011, Marchi et al. 2014, De Stefani et al. 2015).
Efflux of Ca2+ from the matrix to the intermembrane space is catalyzed by the Na+/Ca2+ antiporter SLC8B1 (NCLX) located in the inner membrane. LETM1 is also observed to export calcium from the matrix to the intermembrane space by acting as an H+/Ca2+ antiporter, although somewhat contradictory results have been found in knockdowns of LETM1. Calcium in the intermembrane space may be transported to the cytosol by the Na+/Ca2+ antiporter SLC8A3 (NCX3), however the mitochondrial localization of SLC8A3 is controversial and SLC8A3 has a limited distribution among tissues.
Efflux of Ca2+ from the matrix to the intermembrane space is catalyzed by the Na+/Ca2+ antiporter SLC8B1 (NCLX) located in the inner membrane. LETM1 is also observed to export calcium from the matrix to the intermembrane space by acting as an H+/Ca2+ antiporter, although somewhat contradictory results have been found in knockdowns of LETM1. Calcium in the intermembrane space may be transported to the cytosol by the Na+/Ca2+ antiporter SLC8A3 (NCX3), however the mitochondrial localization of SLC8A3 is controversial and SLC8A3 has a limited distribution among tissues.
所含基因
13 个基因