Mari State University, Yoshkar-Ola, the Mari El Republic, Russia.
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow region, Russia.
Bull Exp Biol Med. 2022 Apr;172(6):695-700. doi: 10.1007/s10517-022-05459-6. Epub 2022 May 2.
We studied the effect of the mitochondrial calcium-dependent pore (MPT pore) inhibitor alisporivir (5 mg/kg per day for 4 weeks) on the parameters of calcium ion transport and the intensity of mitophagy in mitochondria of the heart and skeletal muscles of dystrophin-deficient C57BL/10ScSn-mdx mice. Alisporivir increased the rate of calcium uptake by skeletal muscle mitochondria of mdx mice, which was accompanied by changes in the level of the MCU and MCUb subunits of the calcium uniporter. At the same time, the intensity of calcium uniport in the heart mitochondria did not change. Alisporivir was found to reduce the expression of Pink1 and Parkin genes regulating the intensity of mitophagy in skeletal muscles of mdx mice, but did not affect the expression of these genes in the heart. This effect of alisporivir was accompanied by fragmentation and a decrease in the mean size of organelles. Possible mitochondrion-related mechanisms of the protective effect of alisporivir on the skeletal muscle and heart cells are discussed.
我们研究了线粒体钙依赖性孔（MPT 孔）抑制剂阿里司波韦（每天 5 毫克/千克，持续 4 周）对肌营养不良症缺失型 C57BL/10ScSn-mdx 小鼠心脏和骨骼肌线粒体钙离子转运参数和噬线粒体强度的影响。阿里司波韦增加了 mdx 小鼠骨骼肌线粒体的钙离子摄取率，这伴随着钙单向转运体的 MCU 和 MCUb 亚基水平的变化。同时，心肌线粒体的钙单向转运强度没有变化。研究发现，阿里司波韦降低了调节 mdx 小鼠骨骼肌噬线粒体强度的 Pink1 和 Parkin 基因的表达，但对心脏中这些基因的表达没有影响。阿里司波韦的这种作用伴随着片段化和细胞器平均大小的减少。讨论了阿里司波韦对骨骼肌和心脏细胞的保护作用的可能与线粒体相关的机制。
