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Structural and Functional Features of Ca2+ Transport Systems in Liver Mitochondria of Rats with Experimental Hyperthyroidism
Bulletin of Experimental Biology and Medicine ( IF 0.9 ) Pub Date : 2020-06-01 , DOI: 10.1007/s10517-020-04855-0
N V Belosludtseva 1 , E Yu Talanov 1 , N I Venediktova 1 , M G Sharapov 2 , G D Mironova 1 , K N Belosludtsev 1, 3
Affiliation  

We analyzed structural and functional features of the main mitochondrial Ca2+-transporting systems, mitochondrial Ca2+ uniporter complex (MCUC) and Ca2+-dependent cyclosporin A-sensitive mitochondrial permeability transition pore (MPT pore), in rats with hyperthyroid state. It was found that, the rate of Ca2+ accumulation by rat liver mitochondria in this pathology increases by 1.3 times, which can be associated with higher level of the channel-forming subunit of the uniporter MCU and lower content of dominant-negative subunit of this complex MCUb. At the same time, the level of the regulatory subunit MICU1 remained unchanged. It was shown that calcium retention capacity of liver mitochondria in rats with experimental hyperthyroidism decreased by 2 times in comparison with the control, which attested to reduced resistance of liver mitochondria of hyperthyroid rats to induction of the MPT pore. The observed changes are consistent with the data on increased amount of cyclophilin D, a mitochondrial matrix peptidyl-prolyl isomerase that is known to modulate the MPT pore opening and expression of the Ppif gene that encodes mitochondrial cyclophilin D in rats with experimental hyperthyroidism.

中文翻译:


实验性甲亢大鼠肝线粒体Ca2+转运系统的结构和功能特征



我们分析了甲状腺功能亢进状态大鼠中主要线粒体 Ca2+ 转运系统、线粒体 Ca2+ 单向转运蛋白复合物 (MCUC) 和 Ca2+ 依赖性环孢菌素 A 敏感线粒体通透性转换孔 (MPT 孔) 的结构和功能特征。结果发现,该病理状态下大鼠肝线粒体Ca2+积累率增加1.3倍,这可能与单向转运蛋白MCU的通道形成亚基水平较高和该复合物显性失活亚基含量较低有关MCUb。与此同时,调节亚基MICU1的水平保持不变。结果显示,实验性甲亢大鼠肝线粒体钙保留能力较对照组降低2倍,证明甲亢大鼠肝线粒体对MPT孔诱导的抵抗力降低。观察到的变化与亲环蛋白 D 量增加的数据一致,亲环蛋白 D 是一种线粒体基质肽基-脯氨酰异构酶,已知在实验性甲状腺功能亢进症大鼠中调节 MPT 孔开放和编码线粒体亲环蛋白 D 的 Ppif 基因的表达。
更新日期:2020-06-01
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