Asymmetric Segregation of Age‐Induced Damage in Budding Yeast

Abstract

Cellular damage follows an asymmetric pattern of inheritance in budding yeast. Age‐associated factors accrue in mother cells after each mitotic division, while the ensuing daughter cells are devoid of any damage. Mother cells retain dysfunctional organelles, including oxidised mitochondria, alkaline vacuoles and a nucleus with a weakened permeability barrier. The nucleus of the mother cell contains additional ageing factors such as misfolded proteins, ribosomal DNA (rDNA) circles and fragmented nucleoli. These factors persist throughout replicative ageing and may contribute to cellular senescence. Interestingly, protein aggregates and nucleolar aberrations retained in mitosis are excluded from the meiotic products, also known as gametes. This occurs by a five‐way nuclear division during meiosis II, where the genetic material destined for four gametes is physically separated away from the age‐induced damage through the formation of a fifth nuclear compartment, which eventually gets degraded during gamete maturation. As a result of this specialised nuclear division, meiotic progeny is born young, devoid of any preexisting damage.

Key Concepts

  • Age‐induced damage is asymmetrically retained in mother cells during mitosis.
  • Organelle function declines in mother cells as they undergo replicative aging.
  • A diffusion barrier at the bud neck, the region between the mother and daughter cell, facilitates the retention of nuclear and endoplasmic reticulum (ER) age‐induced damage.
  • Age‐induced damage from mother cells is not passed onto the meiotic products.
  • Gametes generated by old mother cells are rejuvenated and have the same replicative lifespan as gametes generated by young mother cells.

Keywords: asymmetric cell division; replicative lifespan; diffusion barrier; mitosis; meiosis; protein aggregates; nucleolus; meiotic differentiation; cellular rejuvenation; nuclear pore complex; nucleoporin

Figure 1. Asymmetric retention of damage in budding yeast mitosis. Organelle damage, such as fragmented mitochondria and alkaline vacuoles, accumulate in mother cells during replicative ageing (Hughes and Gottschling, ). Other forms of damage exist in the nucleus, including protein aggregates and rDNA circles (Sinclair and Guarente, ; Saarikangas et al., ). Nuclear age‐associated factors are retained in the mother by a nuclear envelope lateral diffusion barrier located at the bud neck (Clay et al., ; Denoth‐Lippuner et al., ).
Figure 2. Asymmetric retention of damage during meiotic differentiation. Nuclear damage, including protein aggregates, rDNA circles and abnormal nucleolar material, are sequestered away from the dividing nuclei during meiosis II. This process is coupled to a nuclear remodelling event that generates the GUNC. This compartment is not inherited by the developing gametes and is subsequently eliminated. Adapted from King et al. ().
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Goodman, Jay S, and Ünal, Elçin(May 2020) Asymmetric Segregation of Age‐Induced Damage in Budding Yeast. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0021856]