Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2025 Feb 10;42(2):198-205. doi: 10.3760/cma.j.cn511374-20221101-00574.
ABSTRACT
OBJECTIVE: To explore the mechanism of BNIP3-mediated mitophagy in m.3635G>A related Leber’s hereditary optic neuropathy (LHON).
METHODS: A trans-mitochondrial 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 trans-mitochondrial 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: 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). 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.
PMID:40350399 | DOI:10.3760/cma.j.cn511374-20221101-00574