Reactive oxygen species generated from the mitochondrial electron transport chain induce cytochrome c dissociation from beef-heart submitochondrial particles via cardiolipin peroxidation. Possible role in the apoptosis.
Cytochrome c release from mitochondria is a critical event in the apoptosis induction. Dissociation of cytochrome c from the mitochondrial inner membrane (IMM) is a necessary first step for cytochrome c release. In the present study, the effect of reactive oxygen species (ROS) on the dissociation of cytochrome c from beef-heart submitochondrial particles (SMP) and on the cardiolipin content was investigated. Exposure of SMP to mitochondrial-mediated ROS generation resulted in a large dissociation of cytochrome c from SMP and in a parallel loss of cardiolipin. Both these effects were directly and significantly correlated and also abolished by superoxide dismutase+catalase. These results demonstrate that ROS generation induces the dissociation of cytochrome c from IMM via cardiolipin peroxidation. The data may prove useful in clarifying the molecular mechanism underlying the release of cytochrome c from the mitochondria to the cytosol.
Petrosillo
G
G
Department of Biochemistry and Molecular Biology and C.N.R Unit for the Study of Mitochondria and Bioenergetics, University of Bari, Via E, Orabona 4, 70126, Bari, Italy.
Ruggiero
F M
FM
Pistolese
M
M
Paradies
G
G
D000818:Animals; D017209:Apoptosis; D002308:Cardiolipins / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D002417:Cattle; D003574:Cytochrome c Group / Q000378:metabolism*; D004579:Electron Transport; D005609:Free Radicals / Q000378:metabolism; D015227:Lipid Peroxidation; D008928:Mitochondria / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
D002308:Cardiolipins; D003574:Cytochrome c Group; D005609:Free Radicals; D017382:Reactive Oxygen Species; D002374:Catalase; D013482:Superoxide Dismutase; D010100:Oxygen