The role of rapamycin in the PINK1/Parkin signaling pathway in mitophagy in podocytes

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-09-09 DOI:10.1515/biol-2022-0958

Shengyou Yu, Weixue Zhu, Li Yu

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Abstract

This study aimed to clarify the role of rapamycin in the PINK1/Parkin signaling pathway in mitophagy in podocytes and the role of voltage-dependent anion channel 1 (VDAC1) in the PINK1/Parkin signaling pathway in mouse glomerular podocytes. For this purpose, podocytes were cultured with rapamycin and observed using microscopy. The apoptosis rate of podocytes was detected by flow cytometry. Changes in the mitochondrial membrane potential were measured. The autophagy-related proteins VDAC1, PINK1, Parkin, and LC3 were detected, and mitochondrial autophagosomes were observed via transmission electron microscopy. In the present study, we demonstrated that the number of podocytes treated with rapamycin was significantly reduced. Compared with those in the control group, the apoptosis rate of podocytes and the degree of mitochondrial membrane potential depolarization were significantly higher. We also found the expression levels of VDAC1, PINK1, Parkin, and LC3 were significantly increased. In the rapamycin-treated group, the numbers of swollen mitochondria and mitochondrial autophagosomes were significantly higher. Finally, we showed that rapamycin can upregulate the expression of VDAC1, PINK1, Parkin, and LC3 in glomerular podocytes, which is correlated with mitophagy. VDAC1 is involved in mitophagy and is related to the PINK1/Parkin signaling pathway, serving as an indicator of mitophagy in podocytes.

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雷帕霉素在荚膜细胞有丝分裂的 PINK1/Parkin 信号通路中的作用

本研究旨在阐明雷帕霉素在 PINK1/Parkin 信号通路中对荚膜细胞有丝分裂的作用，以及电压依赖性阴离子通道 1（VDAC1）在小鼠肾小球荚膜细胞 PINK1/Parkin 信号通路中的作用。为此，用雷帕霉素培养荚膜细胞并用显微镜观察。流式细胞术检测了荚膜细胞的凋亡率。测量了线粒体膜电位的变化。检测了自噬相关蛋白 VDAC1、PINK1、Parkin 和 LC3，并通过透射电子显微镜观察了线粒体自噬体。本研究表明，雷帕霉素治疗组的荚膜细胞数量明显减少。与对照组相比，荚膜细胞的凋亡率和线粒体膜电位去极化程度明显升高。我们还发现 VDAC1、PINK1、Parkin 和 LC3 的表达水平明显升高。在雷帕霉素处理组中，肿胀线粒体和线粒体自噬体的数量明显增加。最后，我们发现雷帕霉素能上调肾小球荚膜细胞中 VDAC1、PINK1、Parkin 和 LC3 的表达，这与有丝分裂相关。VDAC1参与了有丝分裂，并与PINK1/Parkin信号通路相关，可作为荚膜细胞有丝分裂的指标。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.