Summary
Mitochondrial superoxide overproduction is believed to be responsible for the neurotoxicity associated with neurodegeneration. Mitochondria-targeted antioxidants, such as MitoQ, have emerged as potentially effective antioxidant therapies. Methionine sulfoxide reductase A (MsrA) is a key mitochondrial-localized endogenous antioxidative enzyme and it can scavenge oxidizing species by catalyzing the methionine (Met)-centered redox cycle (MCRC). In this study, we observed that the natural L-Met acted as a good scavenger for antimycin A-induced mitochondrial superoxide overproduction in PC12 cells. This antioxidation was largely dependent on the Met oxidase activity of MsrA. S-methyl-L-cysteine (SMLC), a natural analogue of Met that is abundantly found in garlic and cabbage, could activate the Met oxidase activity of MsrA to scavenge free radicals. Furthermore, SMLC protected against antimycin A-induced mitochondrial membrane depolarization and alleviated 1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity. Thus, our data highlighted the possibility for SMLC supplement in the detoxication of mitochondrial damage by activating the Met oxidase activity of MsrA.
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The authors declare that there is no conflict of interest with any financial organization or corporation or individual that can inappropriately influence this work.
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This work was supported by grants from the National Natural Science Foundation of China (No. 81773712, No. 81473198), the Foundation for Innovative Research Groups of NSFC (No. 81721005), the National Basic Research Program of China (973 Program, No. 2014CB744601), Science Fund for Creative Research Groups of the Natural Science Foundation of Hubei Province (No. 2015CFA020) and PCSIRT (No. IRT13016).
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Ni, L., Guan, Xl., Chen, Ff. et al. S-methyl-L-cysteine Protects against Antimycin A-induced Mitochondrial Dysfunction in Neural Cells via Mimicking Endogenous Methionine-centered Redox Cycle. CURR MED SCI 40, 422–433 (2020). https://doi.org/10.1007/s11596-020-2196-y
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DOI: https://doi.org/10.1007/s11596-020-2196-y