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MitoQ通过增强PINK1/帕金介导的线粒体自噬来抑制肝星状细胞活化和肝纤维化。

MitoQ inhibits hepatic stellate cell activation and liver fibrosis by enhancing PINK1/parkin-mediated mitophagy.

作者信息

Dou Shi-Ding, Zhang Jiu-Na, Xie Xiao-Li, Liu Ting, Hu Jun-Li, Jiang Xiao-Yu, Wang Miao-Miao, Jiang Hui-Ding

机构信息

Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Disease, Hebei, China.

Department of Infectious Diseases, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.

出版信息

Open Med (Wars). 2021 Nov 12;16(1):1718-1727. doi: 10.1515/med-2021-0394. eCollection 2021.

DOI:10.1515/med-2021-0394
PMID:34825063
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8590110/
Abstract

Mitophagy affects the activation of hepatic stellate cells (HSCs). Mitochondria-targeted ubiquinone (MitoQ) is a mitochondria-targeted antioxidant that reduces the production of intracellular reactive oxygen species (ROS). However, its relationship with mitophagy remains unclear. This study evaluated mitophagy during HSC activation and the effects of MitoQ on mitophagy in cell culture and in an animal model of the activation of HSCs. We found that MitoQ reduced the activation of HSCs and alleviated hepatic fibrosis. PINK1 (PTEN-induced putative kinase 1) is a putative serine/threonine kinase located in the mitochondria's outer membrane. While the activation of primary HSCs or LX-2 cells was associated with reduced PINK1/parkin-mediated mitophagy, MitoQ reduced intracellular ROS levels, enhanced PINK1/parkin-mediated mitophagy, and inhibited the activation of HSCs. After knocking down the key mitophagy-related protein, PINK1, in LX-2 cells to block mitophagy, MitoQ intervention failed to inhibit HSC activation. Our results showed that MitoQ inhibited the activation of HSCs and alleviated hepatic fibrosis by enhancing PINK1/parkin-mediated mitophagy.

摘要

线粒体自噬影响肝星状细胞（HSCs）的激活。线粒体靶向泛醌（MitoQ）是一种线粒体靶向抗氧化剂，可减少细胞内活性氧（ROS）的产生。然而，其与线粒体自噬的关系仍不清楚。本研究评估了HSC激活过程中的线粒体自噬以及MitoQ在细胞培养和HSC激活动物模型中对线粒体自噬的影响。我们发现MitoQ可降低HSCs的激活并减轻肝纤维化。PINK1（PTEN诱导的假定激酶1）是一种位于线粒体外膜的假定丝氨酸/苏氨酸激酶。虽然原代HSCs或LX-2细胞的激活与PINK1/帕金介导的线粒体自噬减少有关，但MitoQ可降低细胞内ROS水平，增强PINK1/帕金介导的线粒体自噬，并抑制HSCs的激活。在LX-2细胞中敲低关键的线粒体自噬相关蛋白PINK1以阻断线粒体自噬后，MitoQ干预未能抑制HSC激活。我们的结果表明，MitoQ通过增强PINK1/帕金介导的线粒体自噬来抑制HSCs的激活并减轻肝纤维化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ac/8590110/35a450115bc8/j_med-2021-0394-fig004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ac/8590110/46791366ae3d/j_med-2021-0394-fig001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ac/8590110/bab181c4d950/j_med-2021-0394-fig002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ac/8590110/e565f40e1559/j_med-2021-0394-fig003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ac/8590110/35a450115bc8/j_med-2021-0394-fig004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ac/8590110/46791366ae3d/j_med-2021-0394-fig001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ac/8590110/bab181c4d950/j_med-2021-0394-fig002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ac/8590110/e565f40e1559/j_med-2021-0394-fig003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ac/8590110/35a450115bc8/j_med-2021-0394-fig004.jpg

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