دورية أكاديمية
Mitochondrial oxidative stress regulates LonP1-TDP-43 pathway and rises mitochondrial damage in carbon tetrachloride-induced liver fibrosis
| العنوان: | Mitochondrial oxidative stress regulates LonP1-TDP-43 pathway and rises mitochondrial damage in carbon tetrachloride-induced liver fibrosis |
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| المؤلفون: | Shulin Shan, Zhidan Liu, Shuai Wang, Zhaoxiong Liu, Shihua Chao, Cuiqin Zhang, Ming Li, Fuyong Song |
| المصدر: | Ecotoxicology and Environmental Safety, Vol 264, Iss , Pp 115409- (2023) |
| بيانات النشر: | Elsevier, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Environmental pollution LCC:Environmental sciences |
| مصطلحات موضوعية: | LonP1, TDP-43, Mitochondrial dysfunction, Liver fibrosis, Environmental pollution, TD172-193.5, Environmental sciences, GE1-350 |
| الوصف: | Carbon tetrachloride (CCl4)-mediated liver damage has been well recognized, but the sources and mechanisms of mitochondrial damage during this progress still remain poorly understood. Accumulating evidence has revealed that LonP1-TDP-43 pathway affect proper mitochondrial integrity and function in neurodegenerative diseases. The current study aims to investigate whether mitochondrial oxidative stress regulate LonP1-TDP-43 pathway and the possible roles of this pathway in CCl4-driven liver fibrosis. We found that TDP-43 interacted with LonP1 in chronic CCl4 exposure-induced hepatic fibrogenesis. Moreover, CCl4 led to deficiency of LonP1 and excessive accumulation of TDP-43 on mitochondria. Particularly, the gene correlation analysis for liver fibrosis patients RNA sequencing (RNA-seq) results (GSE159676) showed an obvious negative correlation between LonP1 and TDP-43. By contrast, MitoQ enhanced the occurrence of mitochondrial unfolded protein response (mtUPR), especially the activation of LonP1 after CCl4 treatment. Importantly, mitochondrial antioxidant also promoted the degradation of TDP-43 and alleviated mitochondrial damage. In addition, our results showed that CCl4 induced the release of mitochondrial DNA (mtDNA) and effectively elevated cGAS-STING-mediated immune response, which can be inhibited by MitoQ. Finally, MitoQ prevented CCl4-induced liver fibrosis. Together, our study revealed that LonP1-TDP-43 pathway mediated by mitochondrial oxidative stress participated in the progress of CCl4-drived liver fibrosis. Therefore, mitigating or reversing mitochondrial damage through targeting LonP1-TDP-43 pathway may serve as a promising therapeutic strategy for CCl4 exposure-induced liver diseases. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 0147-6513 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S0147651323009132; https://doaj.org/toc/0147-6513 |
| DOI: | 10.1016/j.ecoenv.2023.115409 |
| URL الوصول: | https://doaj.org/article/10d4a5c3a11f4223904232d628ecab9c |
| رقم الأكسشن: | edsdoj.10d4a5c3a11f4223904232d628ecab9c |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 01476513 |
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| DOI: | 10.1016/j.ecoenv.2023.115409 |