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The p66shc Protein: A Mediator of the Programmed Death of an Organism?
Author(s) -
Skulachev Vladimir P.
Publication year - 2000
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1080/713803613
Subject(s) - microbiology and biotechnology , programmed cell death , serine , apoptosis , organism , phosphatidylserine , phosphorylation , biology , reactive oxygen species , signal transducing adaptor protein , phospholipid , biochemistry , membrane , genetics
Recently knockout of the gene encoding an adaptor protein (p66shc) was shown both to prolong the life span of an animal and to prevent apoptosis of cells in response to added H2O2 (Migliaccio et al. [1999] Nature 402, 309?313). A hypothesis is put forward in which p66shc is assumed to be involved in phenoptosis, i.e., programmed death of an organism, mediated by the reactive oxygen species?dependent massive apoptosis in an organ of vital importance. The reactive oxygen species are suggested to oxidize phosphatidyl serine in the inner leaflet of the cell plasma membrane, resulting in appearance of this phospholipid in the outer membrane leaflet, an effect recognized by a special receptor and causing the p66shc phosphorylation at a serine residue. Serine‐phosphorylated p66shc there is proposed to block mitosis and initiate apoptosis. The large‐scale apoptosis leads to phenoptosis and, hence, shortens the life span of the organism.