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. 2004 Nov;5(2):157-67. doi: 10.1016/j.femsyr.2004.05.008.

Abstract

We show that the dominant activated allele of the yeast RAS gene, RAS2(ala18,val19), led to redox imbalance in exponential-phase cells and to excretion of almost all of the cellular glutathione into the medium when the cells reached early-stationary phase. The mitochondria of the mutant stained strongly with dihydrorhodamine 123 (DHR) and the cells displayed a very short mother cell-specific lifespan. Adding 1 mM reduced glutathione (GSH) to the medium partly restored the lifespan. The corresponding RAS2(+) rho-zero strain also displayed a short lifespan, excreted nearly all of its GSH, and stained positively with DHR. Adding 1 mM GSH completely restored the lifespan of the RAS2(+) rho-zero strain to that of the wild-type cells. The double mutant RAS2(ala18,val19) rho-zero cells showed the same lifespan as the RAS2(ala18,val19) cells, and the effect of glutathione in restoring the lifespan was the same, indicating that both mutations shorten lifespan through a similar mechanism. In the RAS2(ala18,val19) mutant strain and its rho-zero derivative we observed for the first time a strong electron spin resonance (ESR) signal characteristic of the superoxide radical anion. The mutant cells were, therefore, producing superoxide in the absence of a complete mitochondrial electron transport chain, pointing to the existence of a possible non-mitochondrial source for ROS generation. Our results indicate that oxidative stress resulting from a disturbance of redox balance can play a major role in mother cell-specific lifespan determination of yeast cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Northern
  • Electron Spin Resonance Spectroscopy
  • Gene Expression Regulation, Fungal / physiology
  • Glutathione / metabolism
  • Microscopy, Fluorescence
  • Mitochondria / metabolism*
  • Mutagenesis
  • Oxidation-Reduction
  • Oxidative Stress / physiology*
  • RNA, Fungal / chemistry
  • RNA, Fungal / genetics
  • Rhodamines / chemistry
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Superoxides / metabolism*
  • ras Proteins / genetics
  • ras Proteins / metabolism*

Substances

  • RNA, Fungal
  • Rhodamines
  • Saccharomyces cerevisiae Proteins
  • dihydrorhodamine 123
  • Superoxides
  • RAS2 protein, S cerevisiae
  • ras Proteins
  • Glutathione