The Mitochondrial Apoptosis-Induced Channel MAC and Bax Channels Are Regulated by Cytochrome C
Li Guo, D Pietkiewicz, M M. Pavlov, John J. Kasianowicz, L M. Dejean, S J. Korsmeyer, B Antonsson, K W. Kinnally
l-2 family proteins regulate the appearance of the high-conductance channel MAC (mitochondrial apoptosis-induced channel) 1 in the outer membranes of mitochondria early in apoptosis and regulate the release of cytochrome c during commitment to apoptosis. Importantly, physiological ( M) levels of cytochrome c modify MAC activity, but another heme protein, hemoglobin, does not. This effect, coupled with the failure of proteoliposomes containing MAC to retain cytochrome c, indicates that cytochrome c, but not hemoglobin, can selectively transit the pore of MAC. Furthermore, MAC detection correlates with Bax content. MAC shares many single channel characteristics with Bax and both activities are reminiscent of the barrel-stave model channel, alamethicin. These findings indicate MAC is the pore through which cytochrome c is released from mitochondria during apoptosis, and suggest that Bax is a likely component of the MAC. Furthermore, cytochrome c modifies MAC conductance in a pore-size dependent manner, suggesting that cytochrome c may exert regulation of its own release from mitochondria.
American Journal of Physiology
apoptosis, ion channels, patch clamp
, Pietkiewicz, D.
, Pavlov, M.
, Kasianowicz, J.
, Dejean, L.
, Korsmeyer, S.
, Antonsson, B.
and Kinnally, K.
The Mitochondrial Apoptosis-Induced Channel MAC and Bax Channels Are Regulated by Cytochrome C, American Journal of Physiology
(Accessed September 22, 2023)