Fusion of Protein Aggregates Facilitates Asymmetric Damage Segregation

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Miguel Coelho - , Max Planck Institute of Molecular Cell Biology and Genetics, Harvard University (Author)
  • Steven J. Lade - , Max-Planck-Institute for the Physics of Complex Systems, Stockholm University (Author)
  • Simon Alberti - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Thilo Gross - , Max-Planck-Institute for the Physics of Complex Systems, University of Bristol (Author)
  • Iva M. Tolić - , Max Planck Institute of Molecular Cell Biology and Genetics, Ruder Boskovic Institute (Author)

Abstract

Asymmetric segregation of damaged proteins at cell division generates a cell that retains damage and a clean cell that supports population survival. In cells that divide asymmetrically, such as Saccharomyces cerevisiae, segregation of damaged proteins is achieved by retention and active transport. We have previously shown that in the symmetrically dividing Schizosaccharomyces pombe there is a transition between symmetric and asymmetric segregation of damaged proteins. Yet how this transition and generation of damage-free cells are achieved remained unknown. Here, by combining in vivo imaging of Hsp104-associated aggregates, a form of damage, with mathematical modeling, we find that fusion of protein aggregates facilitates asymmetric segregation. Our model predicts that, after stress, the increased number of aggregates fuse into a single large unit, which is inherited asymmetrically by one daughter cell, whereas the other one is born clean. We experimentally confirmed that fusion increases segregation asymmetry, for a range of stresses, and identified Hsp16 as a fusion factor. Our work shows that fusion of protein aggregates promotes the formation of damage-free cells. Fusion of cellular factors may represent a general mechanism for their asymmetric segregation at division.

Details

Original languageEnglish
Article numbere1001886
Pages (from-to)1-11
Number of pages11
JournalPLoS biology
Volume12
Issue number6
Publication statusPublished - 2014
Peer-reviewedYes
Externally publishedYes

External IDs

PubMed 24936793
ORCID /0000-0003-4017-6505/work/142253881