title: Restricted access: spatial sequestration of damaged proteins during stress and aging.
abstract: The accumulation of damaged and aggregated proteins is a hallmark of aging and increased proteotoxic stress. To limit the toxicity of damaged and aggregated proteins and to ensure that the damage is not inherited by succeeding cell generations, a system of spatial quality control operates to sequester damaged/aggregated proteins into inclusions at specific protective sites. Such spatial sequestration and asymmetric segregation of damaged proteins have emerged as key processes required for cellular rejuvenation. In this review, we summarize findings on the nature of the different quality control sites identified in yeast, on genetic determinants required for spatial quality control, and on how aggregates are recognized depending on the stress generating them. We also briefly compare the yeast system to spatial quality control in other organisms. The data accumulated demonstrate that spatial quality control involves factors beyond the canonical quality control factors, such as chaperones and proteases, and opens up new venues in approaching how proteotoxicity might be mitigated, or delayed, upon aging.
authors.affiliation: Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden sandra.malmgren.hill@gu.se.
authors.forename: Sandra Malmgren
authors.initials: SM
authors.lastname: Hill
authors.affiliation: Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
authors.forename: Sarah
authors.initials: S
authors.lastname: Hanzén
authors.affiliation: Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Nyström
mesh_terms: D016922:Cellular Senescence / Q000502:physiology*; D056890:Eukaryota / Q000378:metabolism; D002479:Inclusion Bodies / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism; D066329:Protein Aggregates; D017510:Protein Folding; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism*; D013312:Stress, Physiological
chemical_list: D066329:Protein Aggregates; D011506:Proteins
keywords: aging; asymmetric division; protein aggregates; protein quality control; spatial quality control; vesicle trafficking