Asymmetric inheritance of spindle microtubule-organizing centres preserves replicative lifespan

Nat Cell Biol. 2019 Aug;21(8):952-965. doi: 10.1038/s41556-019-0364-8. Epub 2019 Jul 29.


The differential distribution of the microtubule-organizing centres (MTOCs) that orchestrate spindle formation during cell division is a fascinating phenomenon originally described in Saccharomyces cerevisiae and later found to be conserved during stem cell divisions in organisms ranging from Drosophila to humans. Whether predetermined MTOC inheritance patterns fulfil any biological function is however unknown. Using a genetically designed S. cerevisiae strain that displays a constitutively inverted MTOC fate, we demonstrate that the asymmetric segregation of these structures is critical to ensure normal levels of the Sir2 sirtuin and correct localization of the mitochondrial inheritance regulator Mfb1, and therefore to properly distribute functional mitochondria and protein aggregates between the mother and daughter cells. Consequently, interfering with this process severely accelerates cellular ageing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle / physiology
  • Cell Division / physiology
  • DNA Replication / physiology
  • F-Box Proteins / metabolism
  • Longevity / physiology*
  • Microtubule-Organizing Center / metabolism*
  • Microtubules / metabolism*
  • Mitochondria / metabolism
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae / metabolism
  • Sirtuin 2 / metabolism
  • Spindle Apparatus / metabolism*


  • F-Box Proteins
  • Mfb1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae
  • SIR2 protein, S cerevisiae
  • Sirtuin 2