Fusion, fission, and transport control asymmetric inheritance of mitochondria and protein aggregates

J Cell Biol. 2017 Aug 7;216(8):2481-2498. doi: 10.1083/jcb.201611197. Epub 2017 Jun 14.

Abstract

Partitioning of cell organelles and cytoplasmic components determines the fate of daughter cells upon asymmetric division. We studied the role of mitochondria in this process using budding yeast as a model. Anterograde mitochondrial transport is mediated by the myosin motor, Myo2. A genetic screen revealed an unexpected interaction of MYO2 and genes required for mitochondrial fusion. Genetic analyses, live-cell microscopy, and simulations in silico showed that fused mitochondria become critical for inheritance and transport across the bud neck in myo2 mutants. Similarly, fused mitochondria are essential for retention in the mother when bud-directed transport is enforced. Inheritance of a less than critical mitochondrial quantity causes a severe decline of replicative life span of daughter cells. Myo2-dependent mitochondrial distribution also is critical for the capture of heat stress-induced cytosolic protein aggregates and their retention in the mother cell. Together, these data suggest that coordination of mitochondrial transport, fusion, and fission is critical for asymmetric division and rejuvenation of daughter cells.

Publication types

  • Video-Audio Media

MeSH terms

  • Biological Transport
  • Cell Division*
  • Computer Simulation
  • DNA, Fungal / genetics*
  • DNA, Mitochondrial / genetics*
  • Gene Expression Regulation, Fungal
  • Genotype
  • Microscopy, Video
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Mitochondrial Dynamics*
  • Mutation
  • Myosin Heavy Chains / genetics
  • Myosin Heavy Chains / metabolism*
  • Myosin Type V / genetics
  • Myosin Type V / metabolism*
  • Phenotype
  • Protein Aggregates*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Time Factors

Substances

  • DNA, Fungal
  • DNA, Mitochondrial
  • MYO2 protein, S cerevisiae
  • Protein Aggregates
  • Saccharomyces cerevisiae Proteins
  • Myosin Type V
  • Myosin Heavy Chains