title: Phosphatidylserine exposure in Fas type I cells is mitochondria-dependent.
abstract: 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.
authors.affiliation: Institute of Environmental Medicine, Division of Toxicology, Nobels väg 13, Karolinska Institutet, 171 77, Stockholm, Sweden.
authors.forename: Wanlaya
authors.initials: W
authors.lastname: Uthaisang
authors.forename: Leta K
authors.initials: LK
authors.lastname: Nutt
authors.forename: Sten
authors.initials: S
authors.lastname: Orrenius
authors.forename: Bengt
authors.initials: B
authors.lastname: Fadeel
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000911:Antibodies, Monoclonal / Q000378:metabolism; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D053938:DNA Fragmentation; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D010587:Phagocytosis; D010718:Phosphatidylserines / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D008565:Membrane Proteins; D010718:Phosphatidylserines; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D000255:Adenosine Triphosphate; D020169:Caspases