title: Asymmetric damage segregation at cell division via protein aggregate fusion and attachment to organelles.
abstract: The segregation of damaged components at cell division determines the survival and aging of cells. In cells that divide asymmetrically, such as Saccharomyces cerevisiae, aggregated proteins are retained by the mother cell. Yet, where and how aggregation occurs is not known. Recent work by Zhou and collaborators shows that the birth of protein aggregates, under specific stress conditions, requires active translation, and occurs mainly at the endoplasmic reticulum. Later, aggregates move to the mitochondrial surface through fis1-dependent association. During replicative aging, aggregate association with the mother-cell mitochondria contributes to the asymmetric segregation of aggregates, because mitochondria in the daughter cell do not carry aggregates. With increasing age of mother cells, aggregates lose their connection to the mitochondria, and segregation is less asymmetric. Relating these findings to other mechanisms of aggregate segregation in different organisms, we postulate that fusion between aggregates and their tethering to organelles such as the vacuole, nucleus, ER, or mitochondria are common principles that establish asymmetric segregation during stress resistance and aging.
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA.
authors.forename: Miguel
authors.initials: M
authors.lastname: Coelho
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: D000818:Animals; D060049:Asymmetric Cell Division; D002455:Cell Division; D020090:Chromosome Segregation; D006801:Humans; D015388:Organelles / Q000378:metabolism; D066329:Protein Aggregates; D011485:Protein Binding; D021381:Protein Transport
chemical_list: D066329:Protein Aggregates
keywords: asymmetric segregation; endoplasmic reticulum; fusion; mitochondria; organelle tethering; partitioning; protein aggregates; retention; sequestration