Ca2+ imbalance caused by ERdj5 deletion affects mitochondrial fragmentation

Abstract The endoplasmic reticulum (ER) is the organelle responsible for the folding of secretory/membrane proteins and acts as a dynamic calcium ion (Ca2+) store involved in various cellular signalling pathways. Previously, we reported that the ER-resident disulfide reductase ERdj5 is involved in t...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Riyuji Yamashita, Shohei Fujii, Ryo Ushioda, Kazuhiro Nagata
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6657b0bd952e4c00b2a5f5b45c8104c7
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6657b0bd952e4c00b2a5f5b45c8104c7
record_format	dspace
spelling	oai:doaj.org-article:6657b0bd952e4c00b2a5f5b45c8104c72021-11-08T10:46:20ZCa2+ imbalance caused by ERdj5 deletion affects mitochondrial fragmentation10.1038/s41598-021-99980-92045-2322https://doaj.org/article/6657b0bd952e4c00b2a5f5b45c8104c72021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-99980-9https://doaj.org/toc/2045-2322Abstract The endoplasmic reticulum (ER) is the organelle responsible for the folding of secretory/membrane proteins and acts as a dynamic calcium ion (Ca2+) store involved in various cellular signalling pathways. Previously, we reported that the ER-resident disulfide reductase ERdj5 is involved in the ER-associated degradation (ERAD) of misfolded proteins in the ER and the activation of SERCA2b, a Ca2+ pump on the ER membrane. These results highlighted the importance of the regulation of redox activity in both Ca2+ and protein homeostasis in the ER. Here, we show that the deletion of ERdj5 causes an imbalance in intracellular Ca2+ homeostasis, the activation of Drp1, a cytosolic GTPase involved in mitochondrial fission, and finally the aberrant fragmentation of mitochondria, which affects cell viability as well as phenotype with features of cellular senescence. Thus, ERdj5-mediated regulation of intracellular Ca2+ is essential for the maintenance of mitochondrial homeostasis involved in cellular senescence.Riyuji YamashitaShohei FujiiRyo UshiodaKazuhiro NagataNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Riyuji Yamashita Shohei Fujii Ryo Ushioda Kazuhiro Nagata Ca2+ imbalance caused by ERdj5 deletion affects mitochondrial fragmentation
description	Abstract The endoplasmic reticulum (ER) is the organelle responsible for the folding of secretory/membrane proteins and acts as a dynamic calcium ion (Ca2+) store involved in various cellular signalling pathways. Previously, we reported that the ER-resident disulfide reductase ERdj5 is involved in the ER-associated degradation (ERAD) of misfolded proteins in the ER and the activation of SERCA2b, a Ca2+ pump on the ER membrane. These results highlighted the importance of the regulation of redox activity in both Ca2+ and protein homeostasis in the ER. Here, we show that the deletion of ERdj5 causes an imbalance in intracellular Ca2+ homeostasis, the activation of Drp1, a cytosolic GTPase involved in mitochondrial fission, and finally the aberrant fragmentation of mitochondria, which affects cell viability as well as phenotype with features of cellular senescence. Thus, ERdj5-mediated regulation of intracellular Ca2+ is essential for the maintenance of mitochondrial homeostasis involved in cellular senescence.
format	article
author	Riyuji Yamashita Shohei Fujii Ryo Ushioda Kazuhiro Nagata
author_facet	Riyuji Yamashita Shohei Fujii Ryo Ushioda Kazuhiro Nagata
author_sort	Riyuji Yamashita
title	Ca2+ imbalance caused by ERdj5 deletion affects mitochondrial fragmentation
title_short	Ca2+ imbalance caused by ERdj5 deletion affects mitochondrial fragmentation
title_full	Ca2+ imbalance caused by ERdj5 deletion affects mitochondrial fragmentation
title_fullStr	Ca2+ imbalance caused by ERdj5 deletion affects mitochondrial fragmentation
title_full_unstemmed	Ca2+ imbalance caused by ERdj5 deletion affects mitochondrial fragmentation
title_sort	ca2+ imbalance caused by erdj5 deletion affects mitochondrial fragmentation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6657b0bd952e4c00b2a5f5b45c8104c7
work_keys_str_mv	AT riyujiyamashita ca2imbalancecausedbyerdj5deletionaffectsmitochondrialfragmentation AT shoheifujii ca2imbalancecausedbyerdj5deletionaffectsmitochondrialfragmentation AT ryoushioda ca2imbalancecausedbyerdj5deletionaffectsmitochondrialfragmentation AT kazuhironagata ca2imbalancecausedbyerdj5deletionaffectsmitochondrialfragmentation
_version_	1718442622646747136

Ca2+ imbalance caused by ERdj5 deletion affects mitochondrial fragmentation

Ejemplares similares