TY - JOUR
T1 - The role of the mitochondrial apoptosis induced channel MAC in cytochrome c release
AU - Martinez-Caballero, Sonia
AU - Dejean, Laurent M.
AU - Jonas, Elizabeth A.
AU - Kinnally, Kathleen W.
N1 - Funding Information:
This research was supported by NIH grants Nos.GM57249 to KWK and NS45876 to EAJ, and NSF grants MCB-0235834 and INT003797 to KWK. We thank Carmen Mannella (NYS DOH Wadsworth Center) and Yuri Antonenko (Moscow State) for their insightful discussions and Cynthia Hughes for her excellent technical assistance. We thank D. Bredcsen for C5M14.1 cells.
PY - 2005/6
Y1 - 2005/6
N2 - 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.
AB - 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.
KW - Bax
KW - Cytochrome c
KW - Mitochondrial apoptosis-induced channel MAC
KW - Patch clamp
UR - http://www.scopus.com/inward/record.url?scp=26444524046&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=26444524046&partnerID=8YFLogxK
U2 - 10.1007/s10863-005-6570-z
DO - 10.1007/s10863-005-6570-z
M3 - Review article
C2 - 16167172
AN - SCOPUS:26444524046
SN - 0145-479X
VL - 37
SP - 155
EP - 164
JO - Journal of Bioenergetics and Biomembranes
JF - Journal of Bioenergetics and Biomembranes
IS - 3
ER -