Drp1-mediated mitochondrial fission contributes to mitophagy in paraquat-induced neuronal cell damage

Nengzhou Chen; Zhenkun Guo; Zhousong Luo; Fuli Zheng; Wenya Shao; Guangxia Yu; Ping Cai; Siying Wu; Huangyuan Li

doi:10.1016/j.envpol.2020.116413

Drp1-mediated mitochondrial fission contributes to mitophagy in paraquat-induced neuronal cell damage

Environ Pollut. 2021 Mar 1:272:116413. doi: 10.1016/j.envpol.2020.116413. Epub 2020 Dec 31.

Authors

Nengzhou Chen¹, Zhenkun Guo², Zhousong Luo¹, Fuli Zheng³, Wenya Shao¹, Guangxia Yu³, Ping Cai⁴, Siying Wu⁵, Huangyuan Li⁶

Affiliations

¹ Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, 350122, China.
² The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, 350122, China; Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, 350122, China.
³ Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, 350122, China; The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, 350122, China; Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, 350122, China.
⁴ Department of Health Inspection and Quarantine, School of Public Health, Fujian Medical University, Fuzhou, 350122, China.
⁵ The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, 350122, China; Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, 350122, China; Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, 350122, China.
⁶ Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, 350122, China; The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, 350122, China; Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, 350122, China. Electronic address: lhy@fjmu.edu.cn.

PMID: 33422762
DOI: 10.1016/j.envpol.2020.116413

Abstract

Paraquat (PQ) is one of the most widely used herbicides in the world due to its excellent weed control effects. Accumulating evidence has revealed that long-term exposure to PQ can significantly increase the risk of Parkinson's disease (PD). However, the underlying molecular mechanisms are yet to be fully understood. Hence, we investigated the potential role of reactive oxygen species (ROS) and dynamin-related protein 1 (DRP1) in PQ-induced mitophagy, aiming to elaborate on possible molecular mechanisms involved in PQ-triggered neurotoxicity. Our results showed that ROS were increased, mitochondrial membrane potential was decreased at 100, 200, and 300 μM PQ concentrations, and autophagy pathways were activated at a concentration of 100 μM in neuronal cells. In addition, excessive mitophagy was observed in neurons exposed to 300 μM PQ for 24 h. Then, ROS-mediated mitochondrial fission was found to contribute to PQ-induced excessive mitophagy. Moreover, all aforementioned changes were significantly ameliorated by mdivi-1. Thus, our findings provide a novel neurotoxic mechanism and reveal the DRP1-mitochondrial fission pathway as a potential target for treatments of PQ-induced excessive mitophagy, serving as an alternative target for the prevention and treatment of Parkinson's disease. Because harmful substances are transmitted and enriched in the food chain, the toxic effect of environmental paraquat is nonnegligible, and more investigations are needed.

Keywords: DRP1; Mitochondrial fission; Mitophagy; Paraquat; ROS.

MeSH terms

Herbicides* / toxicity
Mitochondrial Dynamics
Mitophagy
Neurons
Paraquat* / toxicity
Reactive Oxygen Species

Substances

Herbicides
Reactive Oxygen Species
Paraquat