title: Fusion of protein aggregates facilitates asymmetric damage segregation.
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.
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany; FAS Center for Systems Biology, Harvard University, Cambridge, Massachusetts, United States of America.
authors.forename: Miguel
authors.initials: M
authors.lastname: Coelho
authors.affiliation: Max Planck Institute for the Physics of Complex Systems, Dresden, Germany; Stockholm Resilience Centre, Stockholm University, Stockholm, Sweden.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Lade
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Alberti
authors.affiliation: Max Planck Institute for the Physics of Complex Systems, Dresden, Germany; Department of Engineering Mathematics, Merchant Venturers School of Engineering, University of Bristol, Bristol, United Kingdom.
authors.forename: Thilo
authors.initials: T
authors.lastname: Gross
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany; Division of Molecular Biology, Ruđer Bošković Institute, Zagreb, Croatia.
authors.forename: Iva M
authors.initials: IM
authors.lastname: Tolić
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D060049:Asymmetric Cell Division; D006360:Heat-Shock Proteins / Q000378:metabolism*; D008954:Models, Biological; D066329:Protein Aggregates; D012568:Schizosaccharomyces; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D013312:Stress, Physiological
chemical_list: D006360:Heat-Shock Proteins; D066329:Protein Aggregates; D029702:Schizosaccharomyces pombe Proteins; D000251:Adenosine Triphosphatases; C546584:HSP104 protein, S pombe