Puerarin alleviates cadmium-induced mitochondrial mass decrease by inhibiting PINK1–Parkin and Nix-mediated mitophagy in rat cortical neurons

• Published in: Ecotoxicology and environmental safety 2022-01, Vol.230, p.113127, Article 113127
• Main Authors: Wen, Shuangquan, Wang, Li, Wang, Tao, Xu, Mingchang, Zhang, Wenhua, Song, Ruilong, Zou, Hui, Gu, Jianhong, Bian, Jianchun, Yuan, Yan, Liu, Zongping
• Format: Article
• Language: English
• Subjects: Cadmium; Mitochondrial mass; Mitophagy; Neuron; Puerarin
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/j.ecoenv.2021.113127

Cadmium (Cd) has well-known central nervous system toxicity, and mitochondria are direct targets of Cd-induced neuronal toxicity. However, how Cd induces mitochondrial mass decrease in terms of its neurotoxic effects remains unknown. Puerarin, an isoflavone extracted from kudzu root, can cross the blood–brain barrier and exert protective effects in nervous system disease. The purpose of the study was to determine the mechanism of Cd-induced mitochondrial mass decrease and the protective role of puerarin in rat cortical neurons. The results indicated that Cd induced mitochondrial mass decrease by activating mitophagy mediated by the PTEN-induced putative kinase protein 1 (PINK1)–E3 ubiquitin ligase (Parkin) and Nip3-like protein X (Nix) pathways in rat cortical neurons. Puerarin improved the Cd-induced decrease in mitochondrial membrane potential (MMP) in vitro, and blocked PINK1–Parkin and Nix-mediated mitophagy, inhibiting Cd-induced mitochondrial mass decrease in rat cortical neurons in vitro and in vivo. In summary, our data clearly indicated that puerarin protects rat cortical neurons against Cd-induced neurotoxicity by ameliorating mitochondrial damage, inhibiting mitophagy-mediated mitochondrial mass decrease. Puerarin appears to have great potential as a neuroprotective agent. •Cadmium exposure induces mitochondrial mass decrease in rat cortical neurons.•Cadmium activates mitophagy mediated by the PINK1–Parkin and Nix pathways.•Puerarin alleviates cadmium-induced mitochondrial mass decrease.•Puerarin blocks cadmium-activated PINK1–Parkin and Nix pathways.