Molecular mechanisms of apoptosis. Structure of cytochrome c-cardiolipin complex

• Published in: Biochemistry (Moscow) Vol. 78; no. 10; pp. 1086 - 1097
• Main Authors: Vladimirov, Yu. A., Proskurnina, E. V., Alekseev, A. V.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.10.2013; Springer; Springer Nature B.V
• Subjects: Apoptosis; Biochemistry; Biological membranes; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Cardiolipins - chemistry; Cardiolipins - metabolism; Catalysis; Cytochrome; Cytochrome c; Cytochromes c - chemistry; Cytochromes c - metabolism; Life Sciences; Lipid Peroxidation; Lipids; Microbiology; Mitochondria; Models, Molecular; Molecular Structure; Peroxidase; Peroxidation; Physiological aspects; Proteins; Review; Russia; cytochrome; peroxidase activity; apoptosis; cardiolipin
• ISSN: 0006-2979; 1608-3040
• DOI: 10.1134/S0006297913100027

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.