Regulation of the mitochondrial apoptosis-induced channel, MAC, by BCL-2 family proteins.
Programmed cell death or apoptosis is central to many physiological processes and pathological conditions such as organogenesis, tissue homeostasis, cancer, and neurodegenerative diseases. Bcl-2 family proteins tightly control this cell death program by regulating the permeabilization of the mitochondrial outer membrane and, hence, the release of cytochrome c and other pro-apoptotic factors. Control of the formation of the mitochondrial apoptosis-induced channel, or MAC, is central to the regulation of apoptosis by Bcl-2 family proteins. MAC is detected early in apoptosis by patch clamping the mitochondrial outer membrane. The focus of this review is on the regulation of MAC activity by Bcl-2 family proteins. The role of MAC as the putative cytochrome c release channel during early apoptosis and insights concerning its molecular composition are also discussed.
Dejean
Laurent M
LM
Department Basic Sciences, New York University, College of Dentistry, 345 East 24th Street, New York, NY 10010, USA.
Martinez-Caballero
Sonia
S
Manon
Stephen
S
Kinnally
Kathleen W
KW
D000818:Animals; D017209:Apoptosis; D051033:Apoptosis Inducing Factor / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000145:classification* / Q000235:genetics / Q000378:metabolism*
D051033:Apoptosis Inducing Factor; D007473:Ion Channels; D019253:Proto-Oncogene Proteins c-bcl-2; D045304:Cytochromes c