A role for divalent metal transporter (DMT1) in mitochondrial uptake of iron and manganese

Abstract Much of iron and manganese metabolism occurs in mitochondria. Uptake of redox-active iron must be tightly controlled, but little is known about how metal ions enter mitochondria. Recently, we established that the divalent metal transporter 1 (DMT1) is present in the outer mitochondrial memb...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Natascha A. Wolff , Michael D. Garrick, Lin Zhao, Laura M. Garrick, Andrew J. Ghio, Frank Thévenod
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c28f4d75b2874b9d9cddc1e25c2f7f68
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c28f4d75b2874b9d9cddc1e25c2f7f68
record_format	dspace
spelling	oai:doaj.org-article:c28f4d75b2874b9d9cddc1e25c2f7f682021-12-02T15:08:16ZA role for divalent metal transporter (DMT1) in mitochondrial uptake of iron and manganese10.1038/s41598-017-18584-42045-2322https://doaj.org/article/c28f4d75b2874b9d9cddc1e25c2f7f682018-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-18584-4https://doaj.org/toc/2045-2322Abstract Much of iron and manganese metabolism occurs in mitochondria. Uptake of redox-active iron must be tightly controlled, but little is known about how metal ions enter mitochondria. Recently, we established that the divalent metal transporter 1 (DMT1) is present in the outer mitochondrial membrane (OMM). Therefore we asked if it mediates Fe2+ and Mn2+ influx. Mitochondria were isolated from HEK293 cells permanently transfected with inducible rat DMT1 isoform 1 A/+IRE (HEK293-rDMT1). Fe2+-induced quenching of the dye PhenGreen™SK (PGSK) occurred in two phases, one of which reflected OMM DMT1 with stronger Fe2+ uptake after DMT1 overexpression. DMT1-specific quenching showed an apparent affinity of ~1.5 µM for Fe2+and was blocked by the DMT1 inhibitor CISMBI. Fe2+ influx reflected an imposed proton gradient, a response that was also observed in purified rat kidney cortex (rKC) mitochondria. Non-heme Fe accumulation assayed by ICPOES and stable 57Fe isotope incorporation by ICPMS were increased in HEK293-rDMT1 mitochondria. HEK293-rDMT1 mitochondria displayed higher 59Fe2+ and 54Mn2+ uptake relative to controls with 54Mn2+ uptake blocked by the DMT1 inhibitor XEN602. Such transport was defective in rKC mitochondria with the Belgrade (G185R) mutation. Thus, these results support a role for DMT1 in mitochondrial Fe2+ and Mn2+ acquisition.Natascha A. Wolff Michael D. GarrickLin ZhaoLaura M. GarrickAndrew J. GhioFrank ThévenodNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Natascha A. Wolff Michael D. Garrick Lin Zhao Laura M. Garrick Andrew J. Ghio Frank Thévenod A role for divalent metal transporter (DMT1) in mitochondrial uptake of iron and manganese
description	Abstract Much of iron and manganese metabolism occurs in mitochondria. Uptake of redox-active iron must be tightly controlled, but little is known about how metal ions enter mitochondria. Recently, we established that the divalent metal transporter 1 (DMT1) is present in the outer mitochondrial membrane (OMM). Therefore we asked if it mediates Fe2+ and Mn2+ influx. Mitochondria were isolated from HEK293 cells permanently transfected with inducible rat DMT1 isoform 1 A/+IRE (HEK293-rDMT1). Fe2+-induced quenching of the dye PhenGreen™SK (PGSK) occurred in two phases, one of which reflected OMM DMT1 with stronger Fe2+ uptake after DMT1 overexpression. DMT1-specific quenching showed an apparent affinity of ~1.5 µM for Fe2+and was blocked by the DMT1 inhibitor CISMBI. Fe2+ influx reflected an imposed proton gradient, a response that was also observed in purified rat kidney cortex (rKC) mitochondria. Non-heme Fe accumulation assayed by ICPOES and stable 57Fe isotope incorporation by ICPMS were increased in HEK293-rDMT1 mitochondria. HEK293-rDMT1 mitochondria displayed higher 59Fe2+ and 54Mn2+ uptake relative to controls with 54Mn2+ uptake blocked by the DMT1 inhibitor XEN602. Such transport was defective in rKC mitochondria with the Belgrade (G185R) mutation. Thus, these results support a role for DMT1 in mitochondrial Fe2+ and Mn2+ acquisition.
format	article
author	Natascha A. Wolff Michael D. Garrick Lin Zhao Laura M. Garrick Andrew J. Ghio Frank Thévenod
author_facet	Natascha A. Wolff Michael D. Garrick Lin Zhao Laura M. Garrick Andrew J. Ghio Frank Thévenod
author_sort	Natascha A. Wolff
title	A role for divalent metal transporter (DMT1) in mitochondrial uptake of iron and manganese
title_short	A role for divalent metal transporter (DMT1) in mitochondrial uptake of iron and manganese
title_full	A role for divalent metal transporter (DMT1) in mitochondrial uptake of iron and manganese
title_fullStr	A role for divalent metal transporter (DMT1) in mitochondrial uptake of iron and manganese
title_full_unstemmed	A role for divalent metal transporter (DMT1) in mitochondrial uptake of iron and manganese
title_sort	role for divalent metal transporter (dmt1) in mitochondrial uptake of iron and manganese
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/c28f4d75b2874b9d9cddc1e25c2f7f68
work_keys_str_mv	AT nataschaawolff arolefordivalentmetaltransporterdmt1inmitochondrialuptakeofironandmanganese AT michaeldgarrick arolefordivalentmetaltransporterdmt1inmitochondrialuptakeofironandmanganese AT linzhao arolefordivalentmetaltransporterdmt1inmitochondrialuptakeofironandmanganese AT lauramgarrick arolefordivalentmetaltransporterdmt1inmitochondrialuptakeofironandmanganese AT andrewjghio arolefordivalentmetaltransporterdmt1inmitochondrialuptakeofironandmanganese AT frankthevenod arolefordivalentmetaltransporterdmt1inmitochondrialuptakeofironandmanganese AT nataschaawolff rolefordivalentmetaltransporterdmt1inmitochondrialuptakeofironandmanganese AT michaeldgarrick rolefordivalentmetaltransporterdmt1inmitochondrialuptakeofironandmanganese AT linzhao rolefordivalentmetaltransporterdmt1inmitochondrialuptakeofironandmanganese AT lauramgarrick rolefordivalentmetaltransporterdmt1inmitochondrialuptakeofironandmanganese AT andrewjghio rolefordivalentmetaltransporterdmt1inmitochondrialuptakeofironandmanganese AT frankthevenod rolefordivalentmetaltransporterdmt1inmitochondrialuptakeofironandmanganese
_version_	1718388211173031936

A role for divalent metal transporter (DMT1) in mitochondrial uptake of iron and manganese

Ejemplares similares