Mitochondrial permeability transition induced by reactive oxygen species is independent of cholesterol‐regulated membrane fluidity

FEBS Letters

Mari, Montserrat¹  Colell, Anna¹  Garcı́a-Ruiz, Carmen¹  Fernández-Checa, José C¹ 

[1] Liver Unit, Institut de Malalties Digestives, Hospital Clı́nic y Provincial, Instituto Investigaciones Biomédicas August Pi Suñer, C/Villarroel 170, 08036 Barcelona, Spain

关键词: Oxidative stress;    Apoptosis;    Caspase;    Glutathione;    Cholesterol;    Mitochondrial glutathione;    Ganglioside GD3;    ANT;    adenine nucleotide translocator;    AIF;    apoptosis-inducing factor;    ATR;    atractyloside;    BHT;    butylated hydroxytoluene;    CHM;    cholesterol-enriched mitochondria;    CSA;    cyclosporin A;    cyt c;    cytochrome c;    DIDS;    4;    4′-diisothiocyanatostilbene-2;    2′-disulfonic acid;    GD3;    ganglioside GD3;    HP;    (R;    S)-3-hydroxy-4-pentenoate;    mGSH;    mitochondrial reduced glutathione;    MPT;    mitochondrial permeability transition;    X+XO;    xanthine plus xanthine oxidase;    VDAC;    voltage-dependent anion channel;   

DOI  :  10.1016/S0014-5793(04)00071-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Cholesterol enrichment of rat liver mitochondria (CHM) impairs atractyloside-induced mitochondrial permeability transition (MPT) due to decreased membrane fluidity. In this study we addressed the effect of cholesterol enrichment on MPT induced by reactive oxygen species (ROS). Superoxide anion generated by xanthine plus xanthine oxidase triggered mitochondrial swelling and cytochrome c release in CHM, which was prevented by butylated hydroxytoluene, an anti-voltage-dependent anion channel antibody, or cyclosporin A. Furthermore, hydrogen peroxide generated by the combination of ganglioside GD3 and mitochondrial GSH depletion elicited mitochondrial swelling and release of cytochrome c, Smac/Diablo and apoptosis-inducing factor in control mitochondria and CHM. Thus, ROS induce MPT and apoptosome activation regardless of decreased mitochondrial membrane dynamics due to cholesterol enrichment.

【 授权许可】

Unknown