Is mitochondrial generation of reactive oxygen species a trigger for autophagy?
Autophagy is a conserved lysosomal degradation pathway that has been extensively studied in recent years. However, the mechanism of autophagy induction is still not clear. Mitochondria are important regulators of both apoptosis and autophagy. One of the triggers for mitochondrial mediated apoptosis is the production of reactive oxygen species (ROS). Recently, several studies have indicated that ROS may be also involved in induction of autophagy. ROS are molecules or ions that are formed by the incomplete one-electron reduction of oxygen, including superoxide (O2 (*-)), hydrogen peroxide (H2O2), hydroxyl radical ((*)OH), nitric oxide (NO), and peroxynitrite (ONOO-). Our recent studies provide strong evidences for the involvement of mitochondrially-generated ROS production in the induction of autophagy as determined by the formation of autophagosomes and autolysosomes. This was accomplished through treatment with mitochondrial toxins that inhibit the electron transport chain in transformed and cancer cells. In addition, we have determined that H2O2 and 2-methoxyestradiol (inhibitor of superoxide dismutases and electron transport chain) induce autophagy leading to cell death. In contrast, normal astrocytes fail to induce autophagy following treatment with mitochondrial toxins. Herein, we discuss several important points of our studies and provide a model for mitochondrially-induced autophagic cell death mediated by ROS.
Chen
Yongqiang
Y
Manitoba Institute of Cell Biology, Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada.
Gibson
Spencer B
SB
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism* / Q000502:physiology*; D008954:Models, Biological; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014118:Toxins, Biological / Q000494:pharmacology
D017382:Reactive Oxygen Species; D014118:Toxins, Biological