Molecular mechanisms of apoptosis. structure of cytochrome c-cardiolipin complex.
One of the functions of cytochrome c in living cells is the initiation of apoptosis by catalyzing lipid peroxidation in the inner mitochondrial membrane, which involves cytochrome c bound with acidic lipids, especially cardiolipin. In this paper the results of studies of cytochrome c-cardiolipin complex structure carried out by different authors mainly on unilamellar cardiolipin-containing phospholipid liposomes are critically analyzed. The principal conclusion from the published papers is that cytochrome c-cardiolipin complex is formed by attachment of a cytochrome c molecule to the membrane surface via electrostatic interactions and the subsequent penetration of one of the fatty-acid cardiolipin chains into the protein globule, this being associated with hydrophobic interactions that break the >Fe·×·S(Met80) coordinate bond and giving rise to appearance of cytochrome c peroxidase activity. Nevertheless, according to data obtained in our laboratory, cytochrome c and cardiolipin form spherical nanoparticles in which protein is surrounded by a monolayer of cardiolipin molecules. Under the action of cooperative forces, the protein in the globule expands greatly in volume, its conformation is modified, and the protein becomes a peroxidase. In extended membranes, such as giant monolayer liposomes, and very likely in biological membranes, the formation of nanospheres of cytochrome c-cardiolipin complex causes fusion of membrane sections and dramatic chaotization of the whole membrane structure. The subsequent disintegration of the outer mitochondrial membrane is accompanied by cytochrome c release from the mitochondria and triggering of a cascade of programmed cell death reactions.
Lomonosov Moscow State University, Faculty of Basic Medicine, Moscow, 117192, Russia. yuvlad@mail.ru.
Yu A
YA
Vladimirov
E V
EV
Proskurnina
A V
AV
Alekseev
D017209:Apoptosis; D002308:Cardiolipins / Q000737:chemistry* / Q000378:metabolism*; D002384:Catalysis; D045304:Cytochromes c / Q000737:chemistry* / Q000378:metabolism*; D015227:Lipid Peroxidation; D008958:Models, Molecular; D015394:Molecular Structure
D002308:Cardiolipins; D045304:Cytochromes c