1. Academic Validation
  2. A pivotal role of selective autophagy in mitochondrial quality control: Implications for zinc oxide nanoparticles induced neurotoxicity

A pivotal role of selective autophagy in mitochondrial quality control: Implications for zinc oxide nanoparticles induced neurotoxicity

  • Chem Biol Interact. 2022 Aug 25;363:110003. doi: 10.1016/j.cbi.2022.110003.
Liwei Wang 1 Zhiyu Duan 1 Madan Liang 1 Chunqiang Wang 2 Tingting Liang 3 Liqian Sun 1 Chaoqun Yan 1 Qingshan Li 4 Taigang Liang 5
Affiliations

Affiliations

  • 1 School of Pharmaceutical Science, Shanxi Medical University, Taiyuan, Shanxi, 030001, China.
  • 2 Department of Critical Care Medicine, The First Affiliated Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030001, China. Electronic address: wangchunqiang86@163.com.
  • 3 Shanxi Provincial Hospital of Chinese Medicine, Taiyuan, Shanxi, 030012, China.
  • 4 School of Pharmaceutical Science, Shanxi Medical University, Taiyuan, Shanxi, 030001, China; Shanxi University of Chinese Medicine, Taiyuan, Shanxi, 030619, China. Electronic address: sxlqs2012@163.com.
  • 5 School of Pharmaceutical Science, Shanxi Medical University, Taiyuan, Shanxi, 030001, China; Shanxi University of Chinese Medicine, Taiyuan, Shanxi, 030619, China. Electronic address: ltaigang@163.com.
Abstract

Excessive occupational, medical, and environmental exposure of zinc oxide nanoparticles (ZnONPs) caused its accumulation in the nervous system and raised global concerns over its detrimental effects. However, very few researches had been conducted on the impact of mitochondrial quality control process on central nervous system (CNS) after ZnONPs administration, including mitochondrial fission, fusion, biogenesis, and Autophagy. In present study, mitochondrial dysfunction and Apoptosis were triggered in ZnONPs-exposed human neuroblastoma SH-SY5Y cells. Upregulation of mitochondrial biogenesis regulator (PGC-1α) and fission proteins (Drp1) and downregulation of fusion proteins (OPA1 and Mfn2) were observed in 3 and 6 μg/mL ZnONPs-treated cells. Meanwhile, loss of mitochondrial dynamics and biogenesis was observed in the severe impaired cells (treated with 12 μg/mL ZnONPs). More, Autophagy and Mitophagy were significantly activated in ZnONPs-treated cells. The increased Beclin1 and LC3 II proteins, decreases of p62 protein, and activated PINK1/Parkin signaling were quantified. The Autophagy agonist (Rapamycin), inhibitor (3-MA), and Mitophagy inhibitor (Cyclosporine A, CsA) were employed to verify the roles of Autophagy and Mitophagy in ZnONPs-treated cells. Consequently, mitochondrial dysfunction and Apoptosis were aggravated by the blockage of Autophagy and Mitophagy. Our research could be used to evaluate the risk assessment of ZnONPs exposure in CNS neurons so as to provide a crucial guideline for their future biological applications.

Keywords

Autophagy; Mitochondrial quality control; Mitophagy; Neurotoxicity; Zinc oxide nanoparticles.

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