Fission Yeast Does Not Age under Favorable Conditions, but Does So after Stress

Abstract

Summary 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.

Dynamic JUNQ inclusion bodies are asymmetrically inherited in mammalian cell lines through the asymmetric partitioning of vimentin

“…In bacteria, for example, aggregated proteins are collected at the old pole of a dividing cell (5). A similar mechanism has been proposed in fission yeast (8). In the budding yeast Saccharomyces cerevisiae, several detailed studies demonstrated interdependence between asymmetric inheritance and the maintenance of the actin cytoskeleton and, in particular, the polarisome complex, which anchors the actin cytoskeleton in the emerging bud (9).…”

A Two-step Protein Quality Control Pathway for a Misfolded DJ-1 Variant in Fission Yeast

“…PABP is a marker of stress granules, RNA-enriched granules that are formed in response to certain stress conditions (38), whereas Hsp104 is a large molecular chaperone involved in protein quality control and disaggregation of various cytosolic protein aggregates (39). To further examine the nature of the observed Sdj1-L169P aggregates, the localization of Sdj1-L169P was analyzed in strains expressing mCherry-labeled PABP (Pab1) or Hsp104.…”

Systematic analysis of asymmetric partitioning of yeast proteome between mother and daughter cells reveals “aging factors” and mechanism of lifespan asymmetry

“…Even in single-celled organisms in which cell division is seemingly morphologically symmetric, such as fission yeast or Escherichia coli, asymmetric partitioning of cellular contents can still occur and have a differential impact on the aging/death fate of the two offspring (4)(5)(6)(7)(8). Asymmetric cell division is also a general phenomenon in mammalian cells (e.g., during development or in mitotically active tissues), where cell division typically leads to two cells with distinct fates, often with different replicative potential.…”