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Restricted access: spatial sequestration of damaged proteins during stress and aging

Forskningsöversiktsartikel
Författare Sandra Malmgren Hill
Sara Hanzén
Thomas Nyström
Publicerad i Embo Reports
Volym 18
Nummer/häfte 3
Sidor 377-391
ISSN 1469-221X
Publiceringsår 2017
Publicerad vid Institutionen för biomedicin
Sidor 377-391
Språk English
Länkar doi.org/10.15252/embr.201643458
Ämnesord aging, asymmetric division, protein aggregates, protein quality control, vesicle trafficking, spatial, alpha-synuclein aggregation, life-span extension, quality-control, saccharomyces-cerevisiae, molecular chaperones, misfolded proteins, actin cytoskeleton, asymmetric inheritance, mutant huntingtin, oxidative, stress, Biochemistry & Molecular Biology, Cell Biology
Ämneskategorier Cellbiologi, Biokemi och molekylärbiologi

Sammanfattning

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.

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