Mitochondrial membrane permeabilization: the sine qua non for cell death.
Mitochondria are essential for maintaining cell life but they also play a role in regulating cell death, which occurs when their membranes become permeabilized. Mitochondria possess two distinct membrane systems including an outer membrane in close communication with the cytosol and an inner membrane involved in energy transduction. Outer membrane permeabilization is regulated by Bcl-2 family proteins, which control the release of proteins from the mitochondrial intermembrane space; these proteins then activate apoptosis. Inner membrane permeabilization is regulated by the mitochondrial permeability transition (MPT), which is activated by calcium and oxidative stress and leads to bioenergetic failure and necrosis. The purpose of this review is to discuss the biochemical mechanisms regulating mitochondrial membrane permeabilization; this is crucial to our understanding of the role of cell death in diseases such as cancer and the neurodegenerative diseases.
Yong Loo Lin School of Medicine, Department of Biochemistry, National University of Singapore, Republic of Singapore. bchjsa@nus.edu.sg
Jeffrey S
JS
Armstrong
D016923:Cell Death; D045304:Cytochromes c / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000378:metabolism; D010084:Oxidation-Reduction; D010539:Permeability; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000737:chemistry
D024101:Mitochondrial Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D013438:Sulfhydryl Compounds; D045304:Cytochromes c