The p66(shc) protein: A mediator of the programmed death of an organism

Recently knockout of the gene encoding an adaptor protein (p66(shc)) was sh own 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, 309-3 13), A hypothesis is put forward in which p66(shc) is assumed to be involve d in phenoptosis, i.e., programmed death of an organism, mediated by the re active oxygen species-dependent massive apoptosis in an organ of vital impo rtance. The reactive oxygen species are suggested to oxidize phosphatidyl s erine in the inner leaflet of the cell plasma membrane, resulting in appear ance of this phospholipid in the outer membrane leaflet, an effect recogniz ed by a special receptor and causing the p66(shc) phosphorylation at a seri ne residue. Serine-phosphorylated p66(shc) there is proposed to block mitos is and initiate apoptosis, The large-scale apoptosis leads to phenoptosis a nd, hence, shortens the life span of the organism.