Drp1缺失通过ABCB10激活线粒体未折叠蛋白反应
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南京医科大学基础医学院神经生物学系

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Drp1 deficiency activates ABCB10-mediated mitochondrial unfolded protein response
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Department of Neurobiology,School of Basic Medicine,Nanjing Medical University

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    摘要:

    目的:在小鼠胚胎成纤维细胞(MEF)中探讨 Drp1缺失激活线粒体未折叠蛋白反应的分子机制。方法:采用不同浓度(0,2.5,5,10mM)的3-NP处理Drp1 KO/KD细胞系、 Drp1抑制剂Mdivi-1或P110处理的MEF细胞系以及对照细胞系,随后进行Western blot检测CHOP、ABCB10,LONP1以及Hsp60的表达。RT-qPCR检测Drp1 KD或Mdivi-1处理后MEF细胞的ABCB10的mRNA水平。结果:3-NP处理的Drp1 KO/KD细胞系以及Mdivi-1和P110处理的MEF细胞系中CHOP表达呈现倍数上调。Drp1 KO/KD细胞系以及Mdivi-1和P110处理的MEF细胞系中ABCB10表达上调,线粒体未折叠蛋白反应效应蛋白LONP1和Hsp60表达上调。同时Drp1 KD细胞系和Mdivi-1处理的MEF细胞系中ABCB10的mRNA水平上调。结论:在MEF细胞中,Drp1表达下调可引起ABCB10表达量增加,导致线粒体未折叠蛋白反应关键蛋白CHOP、LONP1和Hsp60蛋白表达上调,进而激活线粒体未折叠蛋白反应。

    Abstract:

    Objective: To investigate the molecular mechanism of mitochondrial unfolded protein reaction (mtUPR) induced by down-regulation of Drp1 expression in MEF cells. Methods: The expression levels of CHOP, ABCB10, LONP1, and Hsp60 were detected by Western blotting in Drp1 KO/KD cells, MEF cells treated with Drp1 inhibitors Mdivi1 or P110 and control cells after administration of 3-NP at different concentrations (0, 2.5, 5, 10 mM). RT-qPCR was used to detect ABCB10 mRNA levels in Drp1 KD or Mdivi-1 treated MEF cells. Results: The expression levels of CHOP were upregulated in Drp1 KO/KD cells or MEF cells treated with Drp1 inhibitors Mdivi-1 or P110. The expression levels of ABCB10 and mitochondrial unfolded protein response related proteins LONP1 and Hsp60 were upregulated in Drp1 KO/KD cells or MEF cells treated with Drp1 inhibitors Mdivi-1 or P110. Compared with control groups, the mRNA levels of ABCB10 were upregulated in Drp1 KD or Mdivi-1 treated MEF cells. Conclusions: Deficiency of Drp1 activates the mitochondrial unfolded protein response through ABCB10, which causes the upregulation of the mitochondrial unfolded protein reaction proteins CHOP, LONP1 and Hsp60.

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  • 收稿日期:2022-11-19
  • 最后修改日期:2023-02-11
  • 录用日期:2023-05-23
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