Fusion of Protein Aggregates Facilitates Asymmetric Damage Segregation

Miguel Coelho, Stephen J. Lade, Simon Alberti, Thilo Gross, Iva M. Tolic

Research output: Contribution to journalArticle (Academic Journal)peer-review

43 Citations (Scopus)
243 Downloads (Pure)

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.
Original languageEnglish
Article number e1001886
Number of pages11
JournalPLoS Biology
Volume12
Issue number6
DOIs
Publication statusPublished - 17 Jun 2014

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