Loss of molecular interaction between cytochrome c and cardiolipin due to lipid peroxidation.
To explore the molecular mechanism underlying the translocation of cytochrome c from the mitochondrial inner membrane to the cytosol during apoptosis, we analyzed the molecular interaction between cytochrome c and cardiolipin (CL) by (1)H NMR spectroscopy. Bovine heart CL induced a drastic broadening of the linewidth of the downfield signals at 31.4 and 34.2 ppm assigned to the heme methyl group-3 and -8, respectively, of horse heart cytochrome c. In contrast, CL mono- and dihydroperoxides were less active in broadening the signals than CL, and CL trihydroperoxides induced almost no broadening of their linewidth. This finding suggests that the peroxidation of CL induces a release of cytochrome c from mitochondria into the cytosol, which release induces apoptosis in the cells.
Shidoji
Y
Y
Gifu International Institute of Biotechnology, Institute of Applied Biochemistry, Yagi Memorial Park, Mitake, Gifu, 505-0116, Japan.
Hayashi
K
K
Komura
S
S
Ohishi
N
N
Yagi
K
K
D000818:Animals; D017209:Apoptosis; D002308:Cardiolipins / Q000737:chemistry*; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D003574:Cytochrome c Group / Q000737:chemistry*; D006736:Horses; D015227:Lipid Peroxidation; D009682:Magnetic Resonance Spectroscopy; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry; D010545:Peroxides / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet
D002308:Cardiolipins; D003574:Cytochrome c Group; D010545:Peroxides; D010100:Oxygen