Web of Science: 4 citations, Scopus: 4 citations, Google Scholar: citations,
Protein aggregation into insoluble deposits protects from oxidative stress
Carija, Anita (Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Navarro, Susanna (Universitat Autònoma de Barcelona. Departament de Bioquímica i Biomedicina Molecular)
Sánchez de Groot, Natalia (Centre de Regulació Genòmica)
Ventura i Zamora, Salvador (Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")

Date: 2017
Abstract: Protein misfolding and aggregation have been associated with the onset of neurodegenerative disorders. Recent studies demonstrate that the aggregation process can result in a high diversity of protein conformational states, however the identity of the specific species responsible for the cellular damage is still unclear. Here, we use yeast as a model to systematically analyse the intracellular effect of expressing 21 variants of the amyloid-ß-peptide, engineered to cover a continuous range of intrinsic aggregation propensities. We demonstrate the existence of a striking negative correlation between the aggregation propensity of a given variant and the oxidative stress it elicits. Interestingly, each variant generates a specific distribution of protein assemblies in the cell. This allowed us to identify the aggregated species that remain diffusely distributed in the cytosol and are unable to coalesce into large protein inclusions as those causing the highest levels of oxidative damage. Overall, our results indicate that the formation of large insoluble aggregates may act as a protective mechanism to avoid cellular oxidative stress. The scheme represents three different scenarios that can occur in a yeast cell upon Aβ42-GFP peptide expression. Scenario I: Soluble Aβ42-GFP species that neither form protein inclusions, nor diffuse aggregates, are not dangerous for the cell; Scenario II: Aβ42-GFP species that do not form protein inclusions but form diffuse aggregates, which can cause intracellular oxidative stress, are hazardous for the cell; Scenario III: Aβ42-GFP species that form protein inclusions are not deleterious for the cell, suggesting that the formation of these big aggregates acts as a protective strategy against oxidative stress.
Note: Número d'acord de subvenció MINECO/BIO2016-783-78310-R
Note: Número d'acord de subvenció MINECO/BFU2013-44763-P
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades. Creative Commons
Language: Anglès.
Document: article ; recerca ; publishedVersion
Subject: ROS, reactive oxygen species ; FITC, fluorescein isothiocyanate ; FC, flow cytometry ; PI, protein inclusion, PK, proteinase k ; GFP, Green Fluorescent Protein ; IP, propidium iodide ; Protein aggregation ; Oxidative stress ; Amyloid peptide ; Protein inclusions ; Yeast
Published in: Redox Biology, Vol. 12 (Aug. 2017) , p. 699-711, ISSN 2213-2317

PMID: 28410533
DOI: 10.1016/j.redox.2017.03.027


13 p, 1.1 MB

The record appears in these collections:
Articles > Research articles
Articles > Published articles

 Record created 2018-02-08, last modified 2019-02-14



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