Intracytoplasmic Copper Homeostasis Controls Cytochrome <italic toggle="yes">c</italic> Oxidase Production

ABSTRACT Copper is an essential micronutrient used as a metal cofactor by a variety of enzymes, including cytochrome c oxidase (Cox). In all organisms from bacteria to humans, cellular availability and insertion of copper into target proteins are tightly controlled due to its toxicity. The major sub...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Seda Ekici, Serdar Turkarslan, Grzegorz Pawlik, Andrew Dancis, Nitin S. Baliga, Hans-Georg Koch, Fevzi Daldal
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2014
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/835f5793892c47fdace33394a208df11
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:835f5793892c47fdace33394a208df11
record_format	dspace
spelling	oai:doaj.org-article:835f5793892c47fdace33394a208df112021-11-15T15:45:11ZIntracytoplasmic Copper Homeostasis Controls Cytochrome <italic toggle="yes">c</italic> Oxidase Production10.1128/mBio.01055-132150-7511https://doaj.org/article/835f5793892c47fdace33394a208df112014-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01055-13https://doaj.org/toc/2150-7511ABSTRACT Copper is an essential micronutrient used as a metal cofactor by a variety of enzymes, including cytochrome c oxidase (Cox). In all organisms from bacteria to humans, cellular availability and insertion of copper into target proteins are tightly controlled due to its toxicity. The major subunit of Cox contains a copper atom that is required for its catalytic activity. Previously, we identified CcoA (a member of major facilitator superfamily transporters) as a component required for cbb3-type Cox production in the Gram-negative, facultative phototroph Rhodobacter capsulatus. Here, first we demonstrate that CcoA is a cytoplasmic copper importer. Second, we show that bypass suppressors of a ccoA deletion mutant suppress cbb3-Cox deficiency by increasing cellular copper content and sensitivity. Third, we establish that these suppressors are single-base-pair insertion/deletions located in copA, encoding the major P1B-type ATP-dependent copper exporter (CopA) responsible for copper detoxification. A copA deletion alone has no effect on cbb3-Cox biogenesis in an otherwise wild-type background, even though it rescues the cbb3-Cox defect in the absence of CcoA and renders cells sensitive to copper. We conclude that a hitherto unknown functional interplay between the copper importer CcoA and the copper exporter CopA controls intracellular copper homeostasis required for cbb3-Cox production in bacteria like R. capsulatus. IMPORTANCE Copper (Cu) is an essential micronutrient required for many processes in the cell. It is found as a cofactor for heme-copper containing cytochrome c oxidase enzymes at the terminus of the respiratory chains of aerobic organisms by catalyzing reduction of dioxygen (O2) to water. Defects in the biogenesis and copper insertion into cytochrome c oxidases lead to mitochondrial diseases in humans. This work shows that a previously identified Cu transporter (CcoA) is a Cu importer and illustrates the link between two Cu transporters, the importer CcoA and the exporter CopA, required for Cu homeostasis and Cu trafficking to cytochrome c oxidase in the cell.Seda EkiciSerdar TurkarslanGrzegorz PawlikAndrew DancisNitin S. BaligaHans-Georg KochFevzi DaldalAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 5, Iss 1 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Seda Ekici Serdar Turkarslan Grzegorz Pawlik Andrew Dancis Nitin S. Baliga Hans-Georg Koch Fevzi Daldal Intracytoplasmic Copper Homeostasis Controls Cytochrome <italic toggle="yes">c</italic> Oxidase Production
description	ABSTRACT Copper is an essential micronutrient used as a metal cofactor by a variety of enzymes, including cytochrome c oxidase (Cox). In all organisms from bacteria to humans, cellular availability and insertion of copper into target proteins are tightly controlled due to its toxicity. The major subunit of Cox contains a copper atom that is required for its catalytic activity. Previously, we identified CcoA (a member of major facilitator superfamily transporters) as a component required for cbb3-type Cox production in the Gram-negative, facultative phototroph Rhodobacter capsulatus. Here, first we demonstrate that CcoA is a cytoplasmic copper importer. Second, we show that bypass suppressors of a ccoA deletion mutant suppress cbb3-Cox deficiency by increasing cellular copper content and sensitivity. Third, we establish that these suppressors are single-base-pair insertion/deletions located in copA, encoding the major P1B-type ATP-dependent copper exporter (CopA) responsible for copper detoxification. A copA deletion alone has no effect on cbb3-Cox biogenesis in an otherwise wild-type background, even though it rescues the cbb3-Cox defect in the absence of CcoA and renders cells sensitive to copper. We conclude that a hitherto unknown functional interplay between the copper importer CcoA and the copper exporter CopA controls intracellular copper homeostasis required for cbb3-Cox production in bacteria like R. capsulatus. IMPORTANCE Copper (Cu) is an essential micronutrient required for many processes in the cell. It is found as a cofactor for heme-copper containing cytochrome c oxidase enzymes at the terminus of the respiratory chains of aerobic organisms by catalyzing reduction of dioxygen (O2) to water. Defects in the biogenesis and copper insertion into cytochrome c oxidases lead to mitochondrial diseases in humans. This work shows that a previously identified Cu transporter (CcoA) is a Cu importer and illustrates the link between two Cu transporters, the importer CcoA and the exporter CopA, required for Cu homeostasis and Cu trafficking to cytochrome c oxidase in the cell.
format	article
author	Seda Ekici Serdar Turkarslan Grzegorz Pawlik Andrew Dancis Nitin S. Baliga Hans-Georg Koch Fevzi Daldal
author_facet	Seda Ekici Serdar Turkarslan Grzegorz Pawlik Andrew Dancis Nitin S. Baliga Hans-Georg Koch Fevzi Daldal
author_sort	Seda Ekici
title	Intracytoplasmic Copper Homeostasis Controls Cytochrome <italic toggle="yes">c</italic> Oxidase Production
title_short	Intracytoplasmic Copper Homeostasis Controls Cytochrome <italic toggle="yes">c</italic> Oxidase Production
title_full	Intracytoplasmic Copper Homeostasis Controls Cytochrome <italic toggle="yes">c</italic> Oxidase Production
title_fullStr	Intracytoplasmic Copper Homeostasis Controls Cytochrome <italic toggle="yes">c</italic> Oxidase Production
title_full_unstemmed	Intracytoplasmic Copper Homeostasis Controls Cytochrome <italic toggle="yes">c</italic> Oxidase Production
title_sort	intracytoplasmic copper homeostasis controls cytochrome <italic toggle="yes">c</italic> oxidase production
publisher	American Society for Microbiology
publishDate	2014
url	https://doaj.org/article/835f5793892c47fdace33394a208df11
work_keys_str_mv	AT sedaekici intracytoplasmiccopperhomeostasiscontrolscytochromeitalictoggleyescitalicoxidaseproduction AT serdarturkarslan intracytoplasmiccopperhomeostasiscontrolscytochromeitalictoggleyescitalicoxidaseproduction AT grzegorzpawlik intracytoplasmiccopperhomeostasiscontrolscytochromeitalictoggleyescitalicoxidaseproduction AT andrewdancis intracytoplasmiccopperhomeostasiscontrolscytochromeitalictoggleyescitalicoxidaseproduction AT nitinsbaliga intracytoplasmiccopperhomeostasiscontrolscytochromeitalictoggleyescitalicoxidaseproduction AT hansgeorgkoch intracytoplasmiccopperhomeostasiscontrolscytochromeitalictoggleyescitalicoxidaseproduction AT fevzidaldal intracytoplasmiccopperhomeostasiscontrolscytochromeitalictoggleyescitalicoxidaseproduction
_version_	1718427595349950464

Intracytoplasmic Copper Homeostasis Controls Cytochrome <italic toggle="yes">c</italic> Oxidase Production

Ejemplares similares