The role of the mitochondrial apoptosis induced channel MAC in cytochrome c release.
Permeabilization of the mitochondrial outer membrane is a crucial event during apoptosis. It allows the release of proapoptotic factors, like cytochrome c, from the intermembrane space, and represents the commitment step in apoptosis. The mitochondrial apoptosis-induced channel, MAC, is a high-conductance channel that forms during early apoptosis and is the putative cytochrome c release channel. Unlike activation of the permeability transition pore, MAC formation occurs without loss of outer membrane integrity and depolarization. The single channel behavior and pharmacology of reconstituted MAC has been characterized with patch-clamp techniques. Furthermore, MAC's activity is compared to that detected in mitochondria inside the cells at the time cytochrome c is released. Finally, the regulation of MAC by the Bcl-2 family proteins and insights concerning its molecular composition are also discussed.
Martinez-Caballero
Sonia
S
Department of Basic Sciences, New York University College of Dentistry, 345 East 24th Street, New York, NY 10010, USA.
Dejean
Laurent M
LM
Jonas
Elizabeth A
EA
Kinnally
Kathleen W
KW
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D045304:Cytochromes c / Q000378:metabolism*; D006801:Humans; D007473:Ion Channels / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000096:biosynthesis / Q000502:physiology*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology
D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D019253:Proto-Oncogene Proteins c-bcl-2; D045304:Cytochromes c