Mechanism of BNIP3-mediated mitophagy in m. 3635G>A related Leber hereditary optic neuropathy
10.3760/cma.j.cn511374-20221101-00574
- VernacularTitle:BNIP3介导线粒体自噬在m.3635G>A相关Leber遗传性视神经病变中的作用机制
- Author:
Zhen LIU
1
;
Wei GUAN
;
Juanjuan ZHANG
;
Minxin GUAN
Author Information
1. 温州医科大学检验医学院、生命科学学院，Attardi线粒体生物医学研究院，温州 325035
- Publication Type:Journal Article
- Keywords:
Leber hereditary optic neuropathy;
Mitochondrial DNA;
Gene variation;
Autophagy;
Mitophagy
- From:
Chinese Journal of Medical Genetics
2025;42(2):198-205
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the mechanism of BNIP3-mediated mitophagy in m. 3635G>A related Leber′s hereditary optic neuropathy (LHON).Methods:A transmitochondrial cybrid cell line derived from a Chinese LHON patient carrying the m. 3635G>A, diagnosed at the Eye Hospital of Wenzhou Medical University in September 2013, was selected as the study subject. A transmitochondrial cybrid cell line from a healthy control with an identical mitochondrial background was included as a control. Immunofluorescence, real-time quantitative PCR (RT-qPCR), and Western blotting were employed to assess the expression of autophagy-related proteins, aiming to explore the role of BNIP3-mediated mitophagy in m. 3635G>A related LHON. This study was approved by the Medical Ethics Committee of the Eye Hospital of Wenzhou Medical University (Ethics No. 2023-J-096).Results:① Compared with the control group, the protein expression levels of autophagy-related markers LC3 (LC3-Ⅱ/LC3-Ⅰ) and LAMP1 were significantly reduced in the variant group ( P<0.05). Additionally, the protein levels of macroautophagy-related proteins ATG12, ATG7, and ATG5 were also significantly decreased ( P<0.05). ② Compared with the control cells, the mRNA and protein expression levels of mitophagy-associated protein BNIP3 were significantly reduced in the cells of the variant group ( P<0.05). Compared with the control group, both mRNA and protein expression levels of the mitophagy-related protein BNIP3 were significantly reduced in the variant group ( P<0.05). Conclusion:The m. 3635G>A inhibits BNIP3-mediated mitophagy, thereby contributing to the pathogenesis of LHON.
