Transport of Ca2+ and Ca2+-Dependent Permeability Transition in the Liver and Heart Mitochondria of Rats with Different Tolerance to Acute Hypoxia
Transport of Ca2+ and Ca2+-Dependent Permeability Transition in the Liver and Heart Mitochondria of Rats with Different Tolerance to Acute Hypoxia
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DOI：
10.3390/biom10010114
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发表时间：
2020-01-01
期刊：
影响因子：
5.5
通讯作者：
Belosludtseva, Natalia V.
中科院分区：
文献类型：
--
作者：
Belosludtsev, Konstantin N.;Dubinin, Mikhail V.;Belosludtseva, Natalia V.
该工作研究了对急性缺氧高抵抗力（HR）和低抵抗力（LR）大鼠的肝脏和心脏线粒体中通过线粒体钙单向转运蛋白复合物（MCUC）摄取Ca2+以及Ca2+依赖性通透性转换孔（MPT孔）的开放的动力学参数。我们发现HR大鼠肝脏和心脏线粒体对Ca2+的摄取率高于LR大鼠，这与HR大鼠肝线粒体中通道形成亚基MCU含量较高和HR大鼠心脏线粒体中显性失活通道亚基MCUb含量较低有关。结果表明，HR大鼠的肝线粒体比LR大鼠更能抵抗MPT孔的诱导（发现HR大鼠肝线粒体的钙保留能力是LR大鼠的1.3倍）。这些数据与以下事实相关：HR 大鼠肝线粒体中 F0F1-ATP 合酶（MPT 孔的可能结构元件）的水平低于 LR 大鼠。在两种表型大鼠的心脏线粒体中，MPT孔的形成没有显着的统计学差异。该论文讨论了 MCUC 亚基表达的变化和 MPT 孔的假定成分如何影响原本对缺氧耐受性不同以及缺氧引起的组织损伤的动物线粒体的 Ca2+ 稳态。
The work examines the kinetic parameters of Ca2+ uptake via the mitochondrial calcium uniporter complex (MCUC) and the opening of the Ca2+-dependent permeability transition pore (MPT pore) in the liver and heart mitochondria of rats with high resistance (HR) and low resistance (LR) to acute hypoxia. We found that the rate of Ca2+ uptake by mitochondria of the liver and heart in HR rats is higher than that in LR rats, which is associated with a higher level of the channel-forming subunit MCU in liver mitochondria of HR rats and a lower content of the dominant-negative channel subunit MCUb in heart mitochondria of HR rats. It was shown that the liver mitochondria of HR rats are more resistant to the induction of the MPT pore than those of LR rats (the calcium retention capacity of liver mitochondria of HR rats was found to be 1.3 times greater than that of LR rats). These data correlate with the fact that the level of F0F1-ATP synthase, a possible structural element of the MPT pore, in the liver mitochondria of HR rats is lower than in LR rats. In heart mitochondria of rats of the two phenotypes, no statistically significant difference in the formation of the MPT pore was revealed. The paper discusses how changes in the expression of the MCUC subunits and the putative components of the MPT pore can affect Ca2+ homeostasis of mitochondria in animals with originally different tolerance to hypoxia and in hypoxia-induced tissue injury.