Sir2-dependent daughter-to-mother transport
of the damaged proteins in yeast is necessary to prevent high stress
sensitivity of the daughters
D.A. Knorre1,2, S.S. Sokolov1,2,
I.A. Kulemzina3, N.A. Bocharova2,3,
1Belozersky Institute of Physico-Chemical Biology, Moscow State University, Leninskye Gory, 1, Moscow, 119991, Russia
2Institute of Mitoengineering, Moscow State University, Leninskye Gory, 1, Moscow, 119991, Russia
3Department of Bioengineering and Bioinformatics, Moscow State University, Leninskye Gory, 1, Moscow, 119991, Russia
During cell division yeast Saccharomyces cerevisiae distribute intracellular "junk" asymmetrically: carbonylated proteins, extrachromosomal DNA circles are accumulated predominantly in mother cells (Sinclair, Guarente, 1997; Aguilaniu et al., 2003). It is also known that the number of individual divisions for S. cerevisiae cells is limited – a phenomenon called replicative aging. Asymmetrical distribution of the adverse factors was suggested to be responsible for "zeroing" of replicative age of the daughter cells thus preventing the clonal age-dependent decline. Our data suggest another reason why yeast maintain the asymmetry of the damaged intracellular material. We found that acidic stress was about three-fold more harmful for the recently formed daughter cells than for their mothers. A relatively lower stress resistance of the daughters was observed in cells subjected to heat-shock and in cells expressing a fragment of human protein huntingtin with polyglutamine expansion. SIR2 is known to act to maintain the asymmetry between the mother and the bud. Interestingly, under our experimental conditions sir2 knockout appeared to increase the percentage of the inviable daughter cells and to increase the stress resistance of the mothers. We speculate that daughter cells are born more vulnerable to stress conditions than the mothers and that Sir2-dependent asymmetrical distribution of the intracellular "junk" is necessary to diminish the risks for the daughter cells.
The work is supported by Grant of President of Russian Federation MK-4628.2009.4 and RFBR grant 09-04-01704
Sinclair, D.A., Guarente, L. (1997), Cell 91(7):1033-42.
Aguilaniu, H., Gustafsson, L., Rigoulet, M., Nyström, T. (2003) Science 299(5613):1751-3
Homo Sapiens Liberatus Workshop, Moscow State University, May 2010