title: Oxidative signaling pathway for externalization of plasma membrane phosphatidylserine during apoptosis.
abstract: Active maintenance of membrane phospholipid asymmetry is universal in normal cell membranes and its disruption with subsequent externalization of phosphatidylserine is a hallmark of apoptosis. Externalized phosphatidylserine appears to serve as an important signal for targeting recognition and elimination of apoptotic cells by macrophages, however, the molecular mechanisms responsible for phosphatidylserine translocation during apoptosis remain unresolved. Studies have focused on the function of aminophospholipid translocase and phospholipid scramblase as mediators of this process. Here we present evidence that unique oxidative events, represented by selective oxidation of phosphatidylserine, occur during apoptosis that could promote phosphatidylserine externalization. We speculate that selective phosphatidylserine oxidation could affect phosphatidylserine recognition by aminophospholipid translocase and/or directly result in enzyme inhibition. The potential interactions between the anionic phospholipid phosphatidylserine and the redox-active cationic protein effector of apoptosis, cytochrome c, are presented as a potential mechanism to account for selective oxidation of phosphatidylserine during apoptosis. Thus, cytochrome c-mediated phosphatidylserine oxidation may represent an important component of the apoptotic pathway.
authors.affiliation: Department of Environmental and Occupational Health, University of Pittsburgh, 260 Kappa Drive, Pittsburgh, PA 15238, USA. kagan@pitt.edu
authors.forename: V E
authors.initials: VE
authors.lastname: Kagan
authors.forename: J P
authors.initials: JP
authors.lastname: Fabisiak
authors.forename: A A
authors.initials: AA
authors.lastname: Shvedova
authors.forename: Y Y
authors.initials: YY
authors.lastname: Tyurina
authors.forename: V A
authors.initials: VA
authors.lastname: Tyurin
authors.forename: N F
authors.initials: NF
authors.lastname: Schor
authors.forename: K
authors.initials: K
authors.lastname: Kawai
mesh_terms: D000818:Animals; D017209:Apoptosis; D002462:Cell Membrane / Q000378:metabolism*; D003574:Cytochrome c Group / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D010718:Phosphatidylserines / Q000378:metabolism*; D015398:Signal Transduction; D013379:Substrate Specificity
chemical_list: D003574:Cytochrome c Group; D016877:Oxidants; D010718:Phosphatidylserines; D006861:Hydrogen Peroxide