The mitochondrial Cu+ transporter PiC2 (SLC25A3) is a target of MTF1 and contributes to the development of skeletal muscle in vitro

Autores
McCann, Cat; Quinteros, Michael; Adelugba, Ifeoluwa; Morgada, Marcos Nicolás; Castelblanco, Aida R.; Davis, Emily J.; Lanzirotti, Antonio; Hainer, Sarah J.; Vila, Alejandro Jose; Navea, Juan G.; Padilla-Benavides, Teresita
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The loading of copper (Cu) into cytochrome c oxidase (COX) in mitochondria is essential for energy production in cells. Extensive studies have been performed to characterize mitochondrial cuproenzymes that contribute to the metallation of COX, such as Sco1, Sco2, and Cox17. However, limited information is available on the upstream mechanism of Cu transport and delivery to mitochondria, especially through Cu-impermeable membranes, in mammalian cells. The mitochondrial phosphate transporter SLC25A3, also known as PiC2, binds Cu+ and transports the ion through these membranes in eukaryotic cells, ultimately aiding in the metallation of COX. We used the well-established differentiation model of primary myoblasts derived from mouse satellite cells, wherein Cu availability is necessary for growth and maturation, and showed that PiC2 is a target of MTF1, and its expression is both induced during myogenesis and favored by Cu supplementation. PiC2 deletion using CRISPR/Cas9 showed that the transporter is required for proliferation and differentiation of primary myoblasts, as both processes are delayed upon PiC2 knock-out. The effects of PiC2 deletion were rescued by the addition of Cu to the growth medium, implying the deleterious effects of PiC2 knockout in myoblasts may be in part due to a failure to deliver sufficient Cu to the mitochondria, which can be compensated by other mitochondrial cuproproteins. Co-localization and co-immunoprecipitation of PiC2 and COX also suggest that PiC2 may participate upstream in the copper delivery chain into COX, as verified by in vitro Cu+-transfer experiments. These data indicate an important role for PiC2 in both the delivery of Cu to the mitochondria and COX, favoring the differentiation of primary myoblasts.
Fil: McCann, Cat. Wesleyan University; Estados Unidos
Fil: Quinteros, Michael. Wesleyan University; Estados Unidos
Fil: Adelugba, Ifeoluwa. University of Massachussets; Estados Unidos
Fil: Morgada, Marcos Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Castelblanco, Aida R.. Skidmore College; Estados Unidos
Fil: Davis, Emily J.. Skidmore College; Estados Unidos
Fil: Lanzirotti, Antonio. University of Chicago; Estados Unidos
Fil: Hainer, Sarah J.. University of Pittsburgh; Estados Unidos
Fil: Vila, Alejandro Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Navea, Juan G.. Skidmore College; Estados Unidos
Fil: Padilla-Benavides, Teresita. Wesleyan University; Estados Unidos
Materia
COPPER TRANSPORT
CYTOCHROME C OXIDASE
MITOCHONDRIA
MTF1
PIC2
SLC25A3
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/211530
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/211530
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The mitochondrial Cu+ transporter PiC2 (SLC25A3) is a target of MTF1 and contributes to the development of skeletal muscle in vitroMcCann, CatQuinteros, MichaelAdelugba, IfeoluwaMorgada, Marcos NicolásCastelblanco, Aida R.Davis, Emily J.Lanzirotti, AntonioHainer, Sarah J.Vila, Alejandro JoseNavea, Juan G.Padilla-Benavides, TeresitaCOPPER TRANSPORTCYTOCHROME C OXIDASEMITOCHONDRIAMTF1PIC2SLC25A3https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The loading of copper (Cu) into cytochrome c oxidase (COX) in mitochondria is essential for energy production in cells. Extensive studies have been performed to characterize mitochondrial cuproenzymes that contribute to the metallation of COX, such as Sco1, Sco2, and Cox17. However, limited information is available on the upstream mechanism of Cu transport and delivery to mitochondria, especially through Cu-impermeable membranes, in mammalian cells. The mitochondrial phosphate transporter SLC25A3, also known as PiC2, binds Cu+ and transports the ion through these membranes in eukaryotic cells, ultimately aiding in the metallation of COX. We used the well-established differentiation model of primary myoblasts derived from mouse satellite cells, wherein Cu availability is necessary for growth and maturation, and showed that PiC2 is a target of MTF1, and its expression is both induced during myogenesis and favored by Cu supplementation. PiC2 deletion using CRISPR/Cas9 showed that the transporter is required for proliferation and differentiation of primary myoblasts, as both processes are delayed upon PiC2 knock-out. The effects of PiC2 deletion were rescued by the addition of Cu to the growth medium, implying the deleterious effects of PiC2 knockout in myoblasts may be in part due to a failure to deliver sufficient Cu to the mitochondria, which can be compensated by other mitochondrial cuproproteins. Co-localization and co-immunoprecipitation of PiC2 and COX also suggest that PiC2 may participate upstream in the copper delivery chain into COX, as verified by in vitro Cu+-transfer experiments. These data indicate an important role for PiC2 in both the delivery of Cu to the mitochondria and COX, favoring the differentiation of primary myoblasts.Fil: McCann, Cat. Wesleyan University; Estados UnidosFil: Quinteros, Michael. Wesleyan University; Estados UnidosFil: Adelugba, Ifeoluwa. University of Massachussets; Estados UnidosFil: Morgada, Marcos Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Castelblanco, Aida R.. Skidmore College; Estados UnidosFil: Davis, Emily J.. Skidmore College; Estados UnidosFil: Lanzirotti, Antonio. University of Chicago; Estados UnidosFil: Hainer, Sarah J.. University of Pittsburgh; Estados UnidosFil: Vila, Alejandro Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Navea, Juan G.. Skidmore College; Estados UnidosFil: Padilla-Benavides, Teresita. Wesleyan University; Estados UnidosFrontiers Media2022-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/211530McCann, Cat; Quinteros, Michael; Adelugba, Ifeoluwa; Morgada, Marcos Nicolás; Castelblanco, Aida R.; et al.; The mitochondrial Cu+ transporter PiC2 (SLC25A3) is a target of MTF1 and contributes to the development of skeletal muscle in vitro; Frontiers Media; Frontiers in Molecular Biosciences; 9; 11-2022; 1-172296-889XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fmolb.2022.1037941/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fmolb.2022.1037941info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:28:33Zoai:ri.conicet.gov.ar:11336/211530instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:28:33.396CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The mitochondrial Cu+ transporter PiC2 (SLC25A3) is a target of MTF1 and contributes to the development of skeletal muscle in vitro
title The mitochondrial Cu+ transporter PiC2 (SLC25A3) is a target of MTF1 and contributes to the development of skeletal muscle in vitro
spellingShingle The mitochondrial Cu+ transporter PiC2 (SLC25A3) is a target of MTF1 and contributes to the development of skeletal muscle in vitro
McCann, Cat
COPPER TRANSPORT
CYTOCHROME C OXIDASE
MITOCHONDRIA
MTF1
PIC2
SLC25A3
title_short The mitochondrial Cu+ transporter PiC2 (SLC25A3) is a target of MTF1 and contributes to the development of skeletal muscle in vitro
title_full The mitochondrial Cu+ transporter PiC2 (SLC25A3) is a target of MTF1 and contributes to the development of skeletal muscle in vitro
title_fullStr The mitochondrial Cu+ transporter PiC2 (SLC25A3) is a target of MTF1 and contributes to the development of skeletal muscle in vitro
title_full_unstemmed The mitochondrial Cu+ transporter PiC2 (SLC25A3) is a target of MTF1 and contributes to the development of skeletal muscle in vitro
title_sort The mitochondrial Cu+ transporter PiC2 (SLC25A3) is a target of MTF1 and contributes to the development of skeletal muscle in vitro
dc.creator.none.fl_str_mv McCann, Cat
Quinteros, Michael
Adelugba, Ifeoluwa
Morgada, Marcos Nicolás
Castelblanco, Aida R.
Davis, Emily J.
Lanzirotti, Antonio
Hainer, Sarah J.
Vila, Alejandro Jose
Navea, Juan G.
Padilla-Benavides, Teresita
author McCann, Cat
author_facet McCann, Cat
Quinteros, Michael
Adelugba, Ifeoluwa
Morgada, Marcos Nicolás
Castelblanco, Aida R.
Davis, Emily J.
Lanzirotti, Antonio
Hainer, Sarah J.
Vila, Alejandro Jose
Navea, Juan G.
Padilla-Benavides, Teresita
author_role author
author2 Quinteros, Michael
Adelugba, Ifeoluwa
Morgada, Marcos Nicolás
Castelblanco, Aida R.
Davis, Emily J.
Lanzirotti, Antonio
Hainer, Sarah J.
Vila, Alejandro Jose
Navea, Juan G.
Padilla-Benavides, Teresita
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv COPPER TRANSPORT
CYTOCHROME C OXIDASE
MITOCHONDRIA
MTF1
PIC2
SLC25A3
topic COPPER TRANSPORT
CYTOCHROME C OXIDASE
MITOCHONDRIA
MTF1
PIC2
SLC25A3
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The loading of copper (Cu) into cytochrome c oxidase (COX) in mitochondria is essential for energy production in cells. Extensive studies have been performed to characterize mitochondrial cuproenzymes that contribute to the metallation of COX, such as Sco1, Sco2, and Cox17. However, limited information is available on the upstream mechanism of Cu transport and delivery to mitochondria, especially through Cu-impermeable membranes, in mammalian cells. The mitochondrial phosphate transporter SLC25A3, also known as PiC2, binds Cu+ and transports the ion through these membranes in eukaryotic cells, ultimately aiding in the metallation of COX. We used the well-established differentiation model of primary myoblasts derived from mouse satellite cells, wherein Cu availability is necessary for growth and maturation, and showed that PiC2 is a target of MTF1, and its expression is both induced during myogenesis and favored by Cu supplementation. PiC2 deletion using CRISPR/Cas9 showed that the transporter is required for proliferation and differentiation of primary myoblasts, as both processes are delayed upon PiC2 knock-out. The effects of PiC2 deletion were rescued by the addition of Cu to the growth medium, implying the deleterious effects of PiC2 knockout in myoblasts may be in part due to a failure to deliver sufficient Cu to the mitochondria, which can be compensated by other mitochondrial cuproproteins. Co-localization and co-immunoprecipitation of PiC2 and COX also suggest that PiC2 may participate upstream in the copper delivery chain into COX, as verified by in vitro Cu+-transfer experiments. These data indicate an important role for PiC2 in both the delivery of Cu to the mitochondria and COX, favoring the differentiation of primary myoblasts.
Fil: McCann, Cat. Wesleyan University; Estados Unidos
Fil: Quinteros, Michael. Wesleyan University; Estados Unidos
Fil: Adelugba, Ifeoluwa. University of Massachussets; Estados Unidos
Fil: Morgada, Marcos Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Castelblanco, Aida R.. Skidmore College; Estados Unidos
Fil: Davis, Emily J.. Skidmore College; Estados Unidos
Fil: Lanzirotti, Antonio. University of Chicago; Estados Unidos
Fil: Hainer, Sarah J.. University of Pittsburgh; Estados Unidos
Fil: Vila, Alejandro Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Navea, Juan G.. Skidmore College; Estados Unidos
Fil: Padilla-Benavides, Teresita. Wesleyan University; Estados Unidos
description The loading of copper (Cu) into cytochrome c oxidase (COX) in mitochondria is essential for energy production in cells. Extensive studies have been performed to characterize mitochondrial cuproenzymes that contribute to the metallation of COX, such as Sco1, Sco2, and Cox17. However, limited information is available on the upstream mechanism of Cu transport and delivery to mitochondria, especially through Cu-impermeable membranes, in mammalian cells. The mitochondrial phosphate transporter SLC25A3, also known as PiC2, binds Cu+ and transports the ion through these membranes in eukaryotic cells, ultimately aiding in the metallation of COX. We used the well-established differentiation model of primary myoblasts derived from mouse satellite cells, wherein Cu availability is necessary for growth and maturation, and showed that PiC2 is a target of MTF1, and its expression is both induced during myogenesis and favored by Cu supplementation. PiC2 deletion using CRISPR/Cas9 showed that the transporter is required for proliferation and differentiation of primary myoblasts, as both processes are delayed upon PiC2 knock-out. The effects of PiC2 deletion were rescued by the addition of Cu to the growth medium, implying the deleterious effects of PiC2 knockout in myoblasts may be in part due to a failure to deliver sufficient Cu to the mitochondria, which can be compensated by other mitochondrial cuproproteins. Co-localization and co-immunoprecipitation of PiC2 and COX also suggest that PiC2 may participate upstream in the copper delivery chain into COX, as verified by in vitro Cu+-transfer experiments. These data indicate an important role for PiC2 in both the delivery of Cu to the mitochondria and COX, favoring the differentiation of primary myoblasts.
publishDate 2022
dc.date.none.fl_str_mv 2022-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/211530
McCann, Cat; Quinteros, Michael; Adelugba, Ifeoluwa; Morgada, Marcos Nicolás; Castelblanco, Aida R.; et al.; The mitochondrial Cu+ transporter PiC2 (SLC25A3) is a target of MTF1 and contributes to the development of skeletal muscle in vitro; Frontiers Media; Frontiers in Molecular Biosciences; 9; 11-2022; 1-17
2296-889X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/211530
identifier_str_mv McCann, Cat; Quinteros, Michael; Adelugba, Ifeoluwa; Morgada, Marcos Nicolás; Castelblanco, Aida R.; et al.; The mitochondrial Cu+ transporter PiC2 (SLC25A3) is a target of MTF1 and contributes to the development of skeletal muscle in vitro; Frontiers Media; Frontiers in Molecular Biosciences; 9; 11-2022; 1-17
2296-889X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fmolb.2022.1037941/full
info:eu-repo/semantics/altIdentifier/doi/10.3389/fmolb.2022.1037941
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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