ERO1-independent production of H2O2 within the endoplasmic reticulum fuels Prdx4 mediated oxidative protein foldingReportar como inadecuado


ERO1-independent production of H2O2 within the endoplasmic reticulum fuels Prdx4 mediated oxidative protein folding


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Publication Date: 2015-10-26

Alternative Title: An ER source for H2O2

Journal Title: The Journal of Cell Biology

Publisher: Rockefeller University Press

Volume: 211

Issue: 2

Pages: 253-259

Language: English

Type: Article

Metadata: Show full item record

Citation: Konno, T., Pinho Melo, E., Lopes, C., Mehmeti, I., Lenzen, S., Ron, D., & Avezov, E. (2015). ERO1-independent production of H2O2 within the endoplasmic reticulum fuels Prdx4 mediated oxidative protein folding. The Journal of Cell Biology, 211 (2), 253-259.

Description: This is the author accepted manuscript. The final version is available from Rockefeller University Press via http://dx.doi.org/10.1083/jcb.201506123

Abstract: The endoplasmic reticulum (ER) localized peroxiredoxin 4 (PRDX4) supports disulfide bond formation in eukaryotic cells lacking the ER oxidase ERO1. The source of peroxide that fuels PRDX4-mediated disulfide bond formation has remained a mystery, as ERO1 is believed to be a major producer of H2O2 in the ER lumen. We report on a simple kinetic technique to track H2O2 equilibration between cellular compartments suggesting that the ER is relatively isolated from cytosolic or mitochondrial H2O2 pools. Furthermore, expression of an ER-adapted catalase to degrade lumenal H2O2 attenuated PRDX4- mediated disulfide bond formation in cells lacking ERO1, whilst depletion of H2O2 in the cytosol or mitochondria had no similar effect. ER catalase did not effect the slow residual disulfide bond formation in cell lacking both ERO1 and PRDX4. These observations point to exploitation of a hitherto unrecognized lumenal source of H2O2 by PRDX4 and a parallel slow H2O2-independent pathway for disulfide formation.

Sponsorship: Supported by grants from the Wellcome Trust (Wellcome 084812) the European Commission (EU FP7 Beta-Bat No: 277713) and Fundação para a Ciência e Tecnologia, Portugal (PTDC/QUI-BIQ/119677/2010) and, a Wellcome Trust Strategic Award for core facilities to the Cambridge Institute for Medical Research (Wellcome 100140). DR is a Wellcome Trust Principal Research Fellow. TK was supported by Strategic Young Researcher Overseas Visits Program for Accelerating Brain Circulation, Japan Society for the Promotion of Science (JSPS)

Identifiers:

This record's URL: https://www.repository.cam.ac.uk/handle/1810/251062

Rights: Attribution-NonCommercial-ShareAlike 2.0 UK: England & Wales

Licence URL: http://creativecommons.org/licenses/by-nc-sa/2.0/uk/





Autor: Konno, TasukuPinho Melo, EduardoLopes, CarlosMehmeti, IlirLenzen, SigurdRon, DavidAvezov, Edward

Fuente: https://www.repository.cam.ac.uk/handle/1810/251062



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