Cell death regulation by the Bcl-2 protein family in the mitochondria.
An increase in the permeability of the outer mitochondrial membrane is central to apoptotic cell death, since it leads to the release of several apoptogenic factors, such as cytochrome c and Smac/Diablo, into the cytoplasm that activate downstream death programs. During apoptosis, the mitochondria also release AIF and endonuclease G, both of which are translocated to the nucleus and are implicated in apoptotic nuclear changes that occur in a caspase-independent manner. Mitochondrial membrane permeability is directly controlled by the major apoptosis regulator, i.e., the Bcl-2 family of proteins, mainly through regulation of the formation of apoptotic protein-conducting pores in the outer mitochondrial membrane, although the precise molecular mechanisms are still not completely understood. Here, I focus on the mechanisms by which Bcl-2 family members control the permeability of mitochondrial membrane during apoptosis.
Tsujimoto
Yoshihide
Y
Osaka University Graduate School of Medicine, Department of Post-Genomics and Diseases, Laboratory of Molecular Genetics, CREST of Japanese Science and Technology, Suita, Osaka, Japan. tsujimot@gene.med.osaka-u.ac.jp
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002463:Cell Membrane Permeability / Q000502:physiology; D005057:Eukaryotic Cells / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D019253:Proto-Oncogene Proteins c-bcl-2