Mitophagy–lysosomal pathway is involved in silver nanoparticle-induced apoptosis in A549 cells

• Published in: Ecotoxicology and environmental safety Vol. 208; p. 111463
• Main Authors: Li, Jiangyan, Chang, Xiaoru, Shang, Mengting, Niu, Shuyan, Zhang, Wenli, Zhang, Bangyong, Huang, Wenyan, Wu, Tianshu, Zhang, Ting, Tang, Meng, Xue, Yuying
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 15.01.2021; Elsevier
• Subjects: A549 Cells; Apoptosis; Apoptosis - drug effects; Autophagy; Autophagy - drug effects; Caspase 9; Cell Death - drug effects; Humans; Lysosomal; Lysosomes - metabolism; Membrane Potential, Mitochondrial - drug effects; Metal Nanoparticles - toxicity; Mitochondria; Mitochondria - metabolism; Mitophagy - drug effects; Mitophagy - physiology; Reactive Oxygen Species - metabolism; Silver - toxicity; Silver nanoparticle; Ubiquitin-Protein Ligases; Mitochondria; Autophagy; Lysosomal; Silver nanoparticle; Apoptosis
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/j.ecoenv.2020.111463

With the increasing use of silver nanoparticles (AgNPs) in biological materials, the cytotoxicity caused by these particles has attracted much attention. However, the molecular mechanism underlying AgNP cytotoxicity remains unclear. In this study, we aimed to systematically investigate the toxicity induced by AgNP exposure to the lung adenocarcinoma A549 cell line at the subcellular and signaling pathway levels and elucidate the related molecular mechanism. The survival rate of cells exposed to AgNPs at 0, 20, 40, 80, and 160 μg/mL for 24 or 48 h decreased in a dose- and time-dependent manner. AgNPs induced autophagy and mitophagy, determined by the transmission electron microscopy investigation and upregulation of LC3 II/I, p62, PINK1, and Parkin expression levels. AgNP treatment induced lysosomal injury, including the decline of lysosomal membrane integrity and increase in cathepsin B level. The decreased in mitochondrial membrane potential, along with upregulation of cytochrome c, caspases 9 and 3, and BAX/BCL2, further suggested that mitochondrial injury were involved in AgNP-induced apoptosis. In addition, mitochondrial injury may further lead to excessive production of reactive oxygen species and oxidative/ antioxidant imbalance. The results suggested that AgNPs could regulate autophagy via mitochondrial and lysosome injury in A549 cells. The information of the molecular mechanism will provide an experimental basis for the safe application of nanomaterials. ●AgNPs can be transported to entered lysosomal and caused lysosomal damage in A549 cells.●AgNPs damaged mitochondria and induced mitochondrial-dependent apoptosis in A549 cells.●AgNPs induced excessive ROS production and oxidative/anti-oxidation imbalance in A549 cells.●AgNPs induced autophagy, and activated PINK1/Parkin-mediated mitophagy in A549 cells.