coelho2013fission
Fission Yeast Does Not Age under Favorable Conditions, but Does So after Stress
Miguel Coelho, Aygül Dereli, Anett Haese, Sebastian Kühn, Liliana Malinovska, Morgan E. DeSantis, James Shorter, Simon Alberti, Thilo Gross and Iva M. Tolić-Nørrelykke
Current Biology 23, 1844-1852, 2013
Background: Many unicellular organisms age: as time passes, they divide more slowly and ultimately die. In budding yeast, asymmetric segregation of cellular damage results in aging mother cells and rejuvenated daughters. We hypothesize that the organisms in which this asymmetry is lacking, or can be modulated, may not undergo aging. Results: We performed a complete pedigree analysis of microcolonies of the fission yeast Schizosaccharomyces pombe growing from a single cell. When cells were grown under favorable conditions, none of the lineages exhibited aging, which is defined as a consecutive increase in division time and increased death probability. Under favorable conditions, few cells died, and their death was random and sudden rather than following a gradual increase in division time. Cell death correlated with the inheritance of Hsp104-associated protein aggregates. After stress, the cells that inherited large aggregates aged, showing a consecutive increase in division time and an increased death probability. Their sisters, who inherited little or no aggregates, did not age. Conclusions: We conclude that S. pombe does not age under favorable growth conditions, but does so under stress. This transition appears to be passive rather than active and results from the formation of a single large aggregate, which segregates asymmetrically at the subsequent cell division. We argue that this damage-induced asymmetric segregation has evolved to sacrifice some cells so that others may survive unscathed after severe environmental stresses.
Under favorable conditions S. pombe can grow fast enough to dilute misfolded proteins by growth alone, no aging occurs. Under stress conditions, growth is slower and misfolded proteins aggregate in the cell. Once the concentration is high enough these proteins passively aggregate so that they are all inherited by one of the daughter cells in the next division. This causes aging and death of the affected cell, removing the misfolded proteins from the population.
Figure 1: Under favorable conditions S. pombe can grow fast enough to dilute misfolded proteins by growth alone, no aging occurs. Under stress conditions, growth is slower and misfolded proteins aggregate in the cell. Once the concentration is high enough these proteins passively aggregate so that they are all inherited by one of the daughter cells in the next division. This causes aging and death of the affected cell, removing the misfolded proteins from the population.