Superoxide in apoptosis. Mitochondrial generation triggered by cytochrome c loss.
Activation of apoptosis is associated with generation of reactive oxygen species. The present research shows that superoxide is produced by mitochondria isolated from apoptotic cells due to a switch from the normal 4-electron reduction of O2 to a 1-electron reduction when cytochrome c is released from mitochondria. Bcl-2, a protein that protects against apoptosis and blocks cytochrome c release, prevents superoxide production when it is overexpressed. The switch in electron transfer provides a mechanism for redox signaling that is concomitant with cytochrome c-dependent activation of caspases. The block of cytochrome c release provides a mechanism for the apparent antioxidant function of Bcl-2.
Cai
J
J
Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Jones
D P
DP
D017209:Apoptosis; D003574:Cytochrome c Group / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D010084:Oxidation-Reduction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D013997:Time Factors
D003574:Cytochrome c Group; D019253:Proto-Oncogene Proteins c-bcl-2; D013481:Superoxides; D005978:Glutathione; D019311:Staurosporine