Phosphatidylserine exposure in Fas type I cells is mitochondria‐dependent

FEBS Letters

Fadeel, Bengt¹  Uthaisang, Wanlaya¹  Orrenius, Sten¹  Nutt, Leta K¹ 

[1] Institute of Environmental Medicine, Division of Toxicology, Nobels väg 13, Karolinska Institutet, 171 77 Stockholm, Sweden

关键词: Adenosine triphosphate;    Apoptosis;    Bcl-2;    Mitochondrion;    Phagocytosis;    Phosphatidylserine;    Δψ m;    mitochondrial transmembrane potential;    G3PDH;    glyceraldehyde-3-phosphate dehydrogenase;    PS;    phosphatidylserine;    TAMRA;    5(6)-carboxytetramethyl-rhodamine N-hydroxy-succimide ester;    zVAD-fmk;    benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone;   

DOI  :  10.1016/S0014-5793(03)00508-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Previous studies have demonstrated that Fas-triggered activation of effector caspases and subsequent nuclear apoptosis either is mitochondria-independent (type I cells) or relies on mitochondrial amplification of the initial stimulus (type II cells). We show herein that Bcl-2 overexpression in a prototypic type I cell line (SKW6.4) promotes mitochondrial generation of ATP and blocks Fas-triggered plasma membrane externalization of phosphatidylserine (PS). Moreover, overexpression of Bcl-2 attenuates macrophage engulfment of Fas-triggered cells. Fas-mediated DNA fragmentation, on the other hand, remains unaffected in SKW6.4-bcl-2 cells. These studies thus demonstrate that PS externalization and clearance of cell corpses are mitochondria-dependent events, and show that these events can be dissociated from other features of the apoptotic program, in Fas type I cells.

【 授权许可】

Unknown