Mitochondrial Physiology Network 10.9: 121-122 (2005) - download pdf

Mitochondrial functions in yeast aging and apoptosis.

Michael Breitenbach¹, P Laun¹, G Heeren¹, S Jarolim¹, M Rinnerthaler¹, E Palle¹, S Perju¹, F Madeo², S Wissing², WC Burhans³

¹Dept. Cell Biology, Div. Genetics, University of Salzburg, Austria; ²IMB, Univ. Graz, Austria; ³Dept. Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY, USA. - michael.breitenbach@sbg.ac.at

    Yeast mother cell-specific aging is increasingly studied as a model for replicative aging of human cells. Our aim is  to clarify the relationship between oxidative stress, apoptosis and the aging process. The transcriptome of senescent wild type yeast mother cells isolated by elutriation centrifugation was studied and compared with the transcriptome of apoptotic yeast cells of cdc48 TS as well as orc2-1 TS mutant strains. A large overlap of the old cell and apoptotic cell transcripts was revealed, comprising the functional categories DNA repair, oxidative stress defense and mitochondrial functions. Several of the genes identified in this way were deleted and tested for oxidative stress resistance and longevity. Deletion of genes coding for mitochondrial ribosomal proteins generally led to oxidative stress sensitivity, but we found one example that caused resistance and a marked increase in lifespan. We are presently testing co-segregation of these phenotypes in meiotic tetrads and are analyzing the mechanism which is at work in this longevity mutant.

    Recently we started to investigate the yeast member of the highly conserved eukaryotic gene family, TCTP. The TCTP protein shuttles to the mitochondria when the cells are stressed with a mild oxidative treatment which induces apoptosis. Our findings so far indicate that yeast mother cell-specific aging involves an apoptotic process and that mitochondria play a functional role in this process.

1.    Laun P, Pichova A,  Madeo F, Fuchs J, Ellinger A, Kohlwein S, Dawes I,  Fröhlich K, Breitenbach M (2001) Aged  mother cells of Saccharomyces cerevisiae show markers of oxidative stress and apoptosis. Molec. Microbiol. 39: 1166-1173.

2.    Alic N, Higgins VJ, Pichova A, Breitenbach M, Dawes IW (2003) Lipid hydroperoxides activate the mitogen-activated protein kinase Mpk1p in Saccharomyces cerevisiae. J. Biol. Chem. 278: 41849-418455.

3.    Jarolim S, Millen J, Heeren G, Laun P, Goldfarb DS, Breitenbach M (2004) A novel assay for replicative lifespan in Saccharomyces cerevisiae. FEMS Yeast Res. 5: 169-177.

4.    Heeren G, Jarolim S, Laun P, Rinnerthaler M, Stolze K, Perrone G, Kohlwein S, Nohl H, Dawes I, Breitenbach M (2004) The role of respiration, reactive oxygen species and oxidative stress in mother cell-specific ageing of yeast strains defective in the RAS signalling pathway. FEMS Yeast Res. 5: 157-167.

5.    Laun P, Ramachandran L, Jarolim S, Herker E, Liang P, Wang J, Weinberger M, Burhans DT, Suter B, Madeo F, Burhans WC, Breitenbach M (2005) A comparison of the S. cerevisiae aging and apoptotic transcriptome. FEMS Yeast Res. (in press).