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Mitochondrial transfer of α-synuclein mediates carbon disulfide-induced mitochondrial dysfunction and neurotoxicity

Authors :
Zhidan Liu
Shulin Shan
Kang Kang
Shuai Wang
Hui Yong
Yanan Sun
Yao Bai
Fuyong Song
Source :
Ecotoxicology and Environmental Safety, Vol 281, Iss , Pp 116613- (2024)
Publication Year :
2024
Publisher :
Elsevier, 2024.

Abstract

Exposure to carbon disulfide (CS2) is a recognized risk factor in the pathogenesis of Parkinson’s disease, yet the underlying mechanisms of deleterious effects on mitochondrial integrity have remained elusive. Here, through establishing CS2 exposure models in rat and SH-SY5Y cells, we demonstrated that highly expressed α-synuclein (α-Syn) is transferred to mitochondria via membrane proteins such as Tom20 and leads to mitochondrial dysfunction and mitochondrial oxidative stress, which ultimately causes neuronal injury. We first found significant mitochondrial damage and oxidative stress in CS2-exposed rat midbrain and SH-SY5Y cells and showed that mitochondrial oxidative stress was the main factor of mitochondrial damage by Mitoquinone intervention. Further experiments revealed that CS2 exposure led to the accumulation of α-Syn in mitochondria and that α-Syn co-immunoprecipitated with mitochondrial membrane proteins. Finally, the use of an α-Syn inhibitor (ELN484228) and small interfering RNA (siRNA) effectively mitigated the accumulation of α-Syn in neurons, as well as the inhibition of mitochondrial membrane potential, caused by CS2 exposure. In conclusion, our study identifies the translocation of α-Syn to mitochondria and the impairment of mitochondrial function, which has important implications for the broader understanding and treatment of neurodegenerative diseases associated with environmental toxins.

Details

Language :
English
ISSN :
01476513
Volume :
281
Issue :
116613-
Database :
Directory of Open Access Journals
Journal :
Ecotoxicology and Environmental Safety
Publication Type :
Academic Journal
Accession number :
edsdoj.207eeaba7f194fc79cd6d6619c51f13d
Document Type :
article
Full Text :
https://doi.org/10.1016/j.ecoenv.2024.116613