A critical role of superoxide anion in selenite-induced mitophagic cell death.
Mitochondria, which are a major source of intracellular reactive oxygen species (ROS), are extremely vulnerable to oxidative stress. We recently reported that selenite treatment of various glioma cells induced a non-apoptotic cell death accompanied by excessive mitophagy (selective autophagy of damaged mitochondria). Examination of various ROS revealed that the superoxide anion played a key role in selenite-induced mitochondrial damage, mitophagy and cell death. Treatment with superoxide generators (diquat and paraquat) was sufficient to trigger mitophagy in glioma cells. Small interfering RNA-mediated knockdown of ATG6 or ATG7 attenuated selenite-induced mitophagy and cell death, demonstrating that the mitophagic pathway contributes to selenite-induced cell death. The effect of selenite in glioma cells may thus provide an example of superoxide-mediated mitophagic cell death, i.e., cell death caused by excessive mitophagy.
Kim
Eun Hee
EH
Department of Molecular Science & Technology, Institute for Medical Sciences, Ajou University School of Medicine, Suwon, Korea.
Choi
Kyeong Sook
KS
D000970:Antineoplastic Agents / Q000378:metabolism; D016923:Cell Death / Q000502:physiology*; D005910:Glioma / Q000378:metabolism; D006540:Herbicides / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress; D010269:Paraquat / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D018038:Sodium Selenite / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*
D000970:Antineoplastic Agents; D006540:Herbicides; D017382:Reactive Oxygen Species; D013481:Superoxides; D018038:Sodium Selenite; D010269:Paraquat