Homeostasis of the ER redox state subsequent to proteasome inhibition

Abstract Endoplasmic reticulum (ER) maintains within, an oxidative redox state suitable for disulfide bond formation. We monitored the ER redox dynamics subsequent to proteasome inhibition using an ER redox probe ERroGFP S4. Proteasomal inhibition initially led to oxidation of the ER, but gradually...

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Autores principales:	Yuki Oku, Masahiro Kariya, Takaaki Fujimura, Jun Hoseki, Yasuyoshi Sakai
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/df1b35d163c24cf2ac5874699cdd79ea
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spelling	oai:doaj.org-article:df1b35d163c24cf2ac5874699cdd79ea2021-12-02T13:39:56ZHomeostasis of the ER redox state subsequent to proteasome inhibition10.1038/s41598-021-87944-y2045-2322https://doaj.org/article/df1b35d163c24cf2ac5874699cdd79ea2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87944-yhttps://doaj.org/toc/2045-2322Abstract Endoplasmic reticulum (ER) maintains within, an oxidative redox state suitable for disulfide bond formation. We monitored the ER redox dynamics subsequent to proteasome inhibition using an ER redox probe ERroGFP S4. Proteasomal inhibition initially led to oxidation of the ER, but gradually the normal redox state was recovered that further led to a reductive state. These events were found to be concomitant with the increase in the both oxidized and reduced glutathione in the microsomal fraction, with a decrease of total intracellular glutathione. The ER reduction was suppressed by pretreatment of a glutathione synthesis inhibitor or by knockdown of ATF4, which induces glutathione-related genes. These results suggested cellular adaptation of ER redox homeostasis: (1) inhibition of proteasome led to accumulation of misfolded proteins and oxidative state in the ER, and (2) the oxidative ER was then reduced by ATF4 activation, followed by influx of glutathione into the ER.Yuki OkuMasahiro KariyaTakaaki FujimuraJun HosekiYasuyoshi SakaiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yuki Oku Masahiro Kariya Takaaki Fujimura Jun Hoseki Yasuyoshi Sakai Homeostasis of the ER redox state subsequent to proteasome inhibition
description	Abstract Endoplasmic reticulum (ER) maintains within, an oxidative redox state suitable for disulfide bond formation. We monitored the ER redox dynamics subsequent to proteasome inhibition using an ER redox probe ERroGFP S4. Proteasomal inhibition initially led to oxidation of the ER, but gradually the normal redox state was recovered that further led to a reductive state. These events were found to be concomitant with the increase in the both oxidized and reduced glutathione in the microsomal fraction, with a decrease of total intracellular glutathione. The ER reduction was suppressed by pretreatment of a glutathione synthesis inhibitor or by knockdown of ATF4, which induces glutathione-related genes. These results suggested cellular adaptation of ER redox homeostasis: (1) inhibition of proteasome led to accumulation of misfolded proteins and oxidative state in the ER, and (2) the oxidative ER was then reduced by ATF4 activation, followed by influx of glutathione into the ER.
format	article
author	Yuki Oku Masahiro Kariya Takaaki Fujimura Jun Hoseki Yasuyoshi Sakai
author_facet	Yuki Oku Masahiro Kariya Takaaki Fujimura Jun Hoseki Yasuyoshi Sakai
author_sort	Yuki Oku
title	Homeostasis of the ER redox state subsequent to proteasome inhibition
title_short	Homeostasis of the ER redox state subsequent to proteasome inhibition
title_full	Homeostasis of the ER redox state subsequent to proteasome inhibition
title_fullStr	Homeostasis of the ER redox state subsequent to proteasome inhibition
title_full_unstemmed	Homeostasis of the ER redox state subsequent to proteasome inhibition
title_sort	homeostasis of the er redox state subsequent to proteasome inhibition
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/df1b35d163c24cf2ac5874699cdd79ea
work_keys_str_mv	AT yukioku homeostasisoftheerredoxstatesubsequenttoproteasomeinhibition AT masahirokariya homeostasisoftheerredoxstatesubsequenttoproteasomeinhibition AT takaakifujimura homeostasisoftheerredoxstatesubsequenttoproteasomeinhibition AT junhoseki homeostasisoftheerredoxstatesubsequenttoproteasomeinhibition AT yasuyoshisakai homeostasisoftheerredoxstatesubsequenttoproteasomeinhibition
_version_	1718392648042020864

Homeostasis of the ER redox state subsequent to proteasome inhibition

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