Mitochondria-rough-ER contacts in the liver regulate systemic lipid homeostasis

Autores
Anastasia, Irene; Ilacqua, Nicolò; Raimondi, Andrea; Lemieux, Philippe; Ghandehari-Alavijeh, Rana; Faure, Guilhem; Mekhedov, Sergei L.; Williams, Kevin J.; Caicci, Federico; Valle, Giorgio; Giacomello, Marta; Quiroga, Ariel Dario; Lehner, Richard; Miksis, Michael J.; Toth, Katalin; de Aguiar Vallim, Thomas Q.; Koonin, Eugene V.; Scorrano, Luca; Pellegrini, Luca
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Contacts between organelles create microdomains that play major roles in regulating key intracellular activities and signaling pathways, but whether they also regulate systemic functions remains unknown. Here, we report the ultrastructural organization and dynamics of the inter-organellar contact established by sheets of curved rough endoplasmic reticulum closely wrapped around the mitochondria (wrappER). To elucidate the in vivo function of this contact, mouse liver fractions enriched in wrappER-associated mitochondria are analyzed by transcriptomics, proteomics, and lipidomics. The biochemical signature of the wrappER points to a role in the biogenesis of very-low-density lipoproteins (VLDL). Altering wrappER-mitochondria contacts curtails VLDL secretion and increases hepatic fatty acids, lipid droplets, and neutral lipid content. Conversely, acute liver-specific ablation of Mttp, the most upstream regulator of VLDL biogenesis, recapitulates this hepatic dyslipidemia phenotype and promotes remodeling of the wrappER-mitochondria contact. The discovery that liver wrappER-mitochondria contacts participate in VLDL biology suggests an involvement of inter-organelle contacts in systemic lipid homeostasis.
Fil: Anastasia, Irene. Laval University; Canadá. Brain Research Center; Canadá
Fil: Ilacqua, Nicolò. Laval University; Canadá. Brain Research Center; Canadá
Fil: Raimondi, Andrea. San Raffaele Scientific Institute; Italia
Fil: Lemieux, Philippe. Brain Research Center; Canadá
Fil: Ghandehari-Alavijeh, Rana. Brain Research Center; Canadá
Fil: Faure, Guilhem. Broad Institute of MIT and Harvard; Estados Unidos. National Center For Biotechnology Information; Estados Unidos
Fil: Mekhedov, Sergei L.. National Center For Biotechnology Information ; Estados Unidos
Fil: Williams, Kevin J.. University of California at Los Angeles. School of Medicine; Estados Unidos
Fil: Caicci, Federico. Università di Padova; Italia
Fil: Valle, Giorgio. Università di Padova; Italia
Fil: Giacomello, Marta. Università di Padova; Italia
Fil: Quiroga, Ariel Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina. University of Alberta; Canadá
Fil: Lehner, Richard. University of Alberta; Canadá
Fil: Miksis, Michael J.. Northwestern University; Estados Unidos
Fil: Toth, Katalin. University of Ottawa; Canadá
Fil: de Aguiar Vallim, Thomas Q.. University of California at Los Angeles. School of Medicine; Estados Unidos
Fil: Koonin, Eugene V.. National Center For Biotechnology Information ; Estados Unidos
Fil: Scorrano, Luca. Università di Padova; Italia
Fil: Pellegrini, Luca. Laval University; Canadá
Materia
ENDOPLASMIC RETICULUM
INTER-ORGANELLE CONTACT
LIPOPROTEIN
LIVER METABOLISM
MAM
MITOCHONDRIA
MUP
RRBP1
VLDL
WRAPPER
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/173327
Acceder
id CONICETDig_36b327c154c11df30afe9d8193abcfe0
oai_identifier_str oai:ri.conicet.gov.ar:11336/173327
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Mitochondria-rough-ER contacts in the liver regulate systemic lipid homeostasisAnastasia, IreneIlacqua, NicolòRaimondi, AndreaLemieux, PhilippeGhandehari-Alavijeh, RanaFaure, GuilhemMekhedov, Sergei L.Williams, Kevin J.Caicci, FedericoValle, GiorgioGiacomello, MartaQuiroga, Ariel DarioLehner, RichardMiksis, Michael J.Toth, Katalinde Aguiar Vallim, Thomas Q.Koonin, Eugene V.Scorrano, LucaPellegrini, LucaENDOPLASMIC RETICULUMINTER-ORGANELLE CONTACTLIPOPROTEINLIVER METABOLISMMAMMITOCHONDRIAMUPRRBP1VLDLWRAPPERhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Contacts between organelles create microdomains that play major roles in regulating key intracellular activities and signaling pathways, but whether they also regulate systemic functions remains unknown. Here, we report the ultrastructural organization and dynamics of the inter-organellar contact established by sheets of curved rough endoplasmic reticulum closely wrapped around the mitochondria (wrappER). To elucidate the in vivo function of this contact, mouse liver fractions enriched in wrappER-associated mitochondria are analyzed by transcriptomics, proteomics, and lipidomics. The biochemical signature of the wrappER points to a role in the biogenesis of very-low-density lipoproteins (VLDL). Altering wrappER-mitochondria contacts curtails VLDL secretion and increases hepatic fatty acids, lipid droplets, and neutral lipid content. Conversely, acute liver-specific ablation of Mttp, the most upstream regulator of VLDL biogenesis, recapitulates this hepatic dyslipidemia phenotype and promotes remodeling of the wrappER-mitochondria contact. The discovery that liver wrappER-mitochondria contacts participate in VLDL biology suggests an involvement of inter-organelle contacts in systemic lipid homeostasis.Fil: Anastasia, Irene. Laval University; Canadá. Brain Research Center; CanadáFil: Ilacqua, Nicolò. Laval University; Canadá. Brain Research Center; CanadáFil: Raimondi, Andrea. San Raffaele Scientific Institute; ItaliaFil: Lemieux, Philippe. Brain Research Center; CanadáFil: Ghandehari-Alavijeh, Rana. Brain Research Center; CanadáFil: Faure, Guilhem. Broad Institute of MIT and Harvard; Estados Unidos. National Center For Biotechnology Information; Estados UnidosFil: Mekhedov, Sergei L.. National Center For Biotechnology Information ; Estados UnidosFil: Williams, Kevin J.. University of California at Los Angeles. School of Medicine; Estados UnidosFil: Caicci, Federico. Università di Padova; ItaliaFil: Valle, Giorgio. Università di Padova; ItaliaFil: Giacomello, Marta. Università di Padova; ItaliaFil: Quiroga, Ariel Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina. University of Alberta; CanadáFil: Lehner, Richard. University of Alberta; CanadáFil: Miksis, Michael J.. Northwestern University; Estados UnidosFil: Toth, Katalin. University of Ottawa; CanadáFil: de Aguiar Vallim, Thomas Q.. University of California at Los Angeles. School of Medicine; Estados UnidosFil: Koonin, Eugene V.. National Center For Biotechnology Information ; Estados UnidosFil: Scorrano, Luca. Università di Padova; ItaliaFil: Pellegrini, Luca. Laval University; CanadáCell Press2021-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/173327Anastasia, Irene; Ilacqua, Nicolò; Raimondi, Andrea; Lemieux, Philippe; Ghandehari-Alavijeh, Rana; et al.; Mitochondria-rough-ER contacts in the liver regulate systemic lipid homeostasis; Cell Press; Cell Reports; 34; 11; 3-2021; 1-292211-1247CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.cell.com/cell-reports/fulltext/S2211-1247(21)00187-Xinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2021.108873info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:44:22Zoai:ri.conicet.gov.ar:11336/173327instacron: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:34982025-09-03 09:44:22.562CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Mitochondria-rough-ER contacts in the liver regulate systemic lipid homeostasis
title Mitochondria-rough-ER contacts in the liver regulate systemic lipid homeostasis
spellingShingle Mitochondria-rough-ER contacts in the liver regulate systemic lipid homeostasis
Anastasia, Irene
ENDOPLASMIC RETICULUM
INTER-ORGANELLE CONTACT
LIPOPROTEIN
LIVER METABOLISM
MAM
MITOCHONDRIA
MUP
RRBP1
VLDL
WRAPPER
title_short Mitochondria-rough-ER contacts in the liver regulate systemic lipid homeostasis
title_full Mitochondria-rough-ER contacts in the liver regulate systemic lipid homeostasis
title_fullStr Mitochondria-rough-ER contacts in the liver regulate systemic lipid homeostasis
title_full_unstemmed Mitochondria-rough-ER contacts in the liver regulate systemic lipid homeostasis
title_sort Mitochondria-rough-ER contacts in the liver regulate systemic lipid homeostasis
dc.creator.none.fl_str_mv Anastasia, Irene
Ilacqua, Nicolò
Raimondi, Andrea
Lemieux, Philippe
Ghandehari-Alavijeh, Rana
Faure, Guilhem
Mekhedov, Sergei L.
Williams, Kevin J.
Caicci, Federico
Valle, Giorgio
Giacomello, Marta
Quiroga, Ariel Dario
Lehner, Richard
Miksis, Michael J.
Toth, Katalin
de Aguiar Vallim, Thomas Q.
Koonin, Eugene V.
Scorrano, Luca
Pellegrini, Luca
author Anastasia, Irene
author_facet Anastasia, Irene
Ilacqua, Nicolò
Raimondi, Andrea
Lemieux, Philippe
Ghandehari-Alavijeh, Rana
Faure, Guilhem
Mekhedov, Sergei L.
Williams, Kevin J.
Caicci, Federico
Valle, Giorgio
Giacomello, Marta
Quiroga, Ariel Dario
Lehner, Richard
Miksis, Michael J.
Toth, Katalin
de Aguiar Vallim, Thomas Q.
Koonin, Eugene V.
Scorrano, Luca
Pellegrini, Luca
author_role author
author2 Ilacqua, Nicolò
Raimondi, Andrea
Lemieux, Philippe
Ghandehari-Alavijeh, Rana
Faure, Guilhem
Mekhedov, Sergei L.
Williams, Kevin J.
Caicci, Federico
Valle, Giorgio
Giacomello, Marta
Quiroga, Ariel Dario
Lehner, Richard
Miksis, Michael J.
Toth, Katalin
de Aguiar Vallim, Thomas Q.
Koonin, Eugene V.
Scorrano, Luca
Pellegrini, Luca
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ENDOPLASMIC RETICULUM
INTER-ORGANELLE CONTACT
LIPOPROTEIN
LIVER METABOLISM
MAM
MITOCHONDRIA
MUP
RRBP1
VLDL
WRAPPER
topic ENDOPLASMIC RETICULUM
INTER-ORGANELLE CONTACT
LIPOPROTEIN
LIVER METABOLISM
MAM
MITOCHONDRIA
MUP
RRBP1
VLDL
WRAPPER
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Contacts between organelles create microdomains that play major roles in regulating key intracellular activities and signaling pathways, but whether they also regulate systemic functions remains unknown. Here, we report the ultrastructural organization and dynamics of the inter-organellar contact established by sheets of curved rough endoplasmic reticulum closely wrapped around the mitochondria (wrappER). To elucidate the in vivo function of this contact, mouse liver fractions enriched in wrappER-associated mitochondria are analyzed by transcriptomics, proteomics, and lipidomics. The biochemical signature of the wrappER points to a role in the biogenesis of very-low-density lipoproteins (VLDL). Altering wrappER-mitochondria contacts curtails VLDL secretion and increases hepatic fatty acids, lipid droplets, and neutral lipid content. Conversely, acute liver-specific ablation of Mttp, the most upstream regulator of VLDL biogenesis, recapitulates this hepatic dyslipidemia phenotype and promotes remodeling of the wrappER-mitochondria contact. The discovery that liver wrappER-mitochondria contacts participate in VLDL biology suggests an involvement of inter-organelle contacts in systemic lipid homeostasis.
Fil: Anastasia, Irene. Laval University; Canadá. Brain Research Center; Canadá
Fil: Ilacqua, Nicolò. Laval University; Canadá. Brain Research Center; Canadá
Fil: Raimondi, Andrea. San Raffaele Scientific Institute; Italia
Fil: Lemieux, Philippe. Brain Research Center; Canadá
Fil: Ghandehari-Alavijeh, Rana. Brain Research Center; Canadá
Fil: Faure, Guilhem. Broad Institute of MIT and Harvard; Estados Unidos. National Center For Biotechnology Information; Estados Unidos
Fil: Mekhedov, Sergei L.. National Center For Biotechnology Information ; Estados Unidos
Fil: Williams, Kevin J.. University of California at Los Angeles. School of Medicine; Estados Unidos
Fil: Caicci, Federico. Università di Padova; Italia
Fil: Valle, Giorgio. Università di Padova; Italia
Fil: Giacomello, Marta. Università di Padova; Italia
Fil: Quiroga, Ariel Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina. University of Alberta; Canadá
Fil: Lehner, Richard. University of Alberta; Canadá
Fil: Miksis, Michael J.. Northwestern University; Estados Unidos
Fil: Toth, Katalin. University of Ottawa; Canadá
Fil: de Aguiar Vallim, Thomas Q.. University of California at Los Angeles. School of Medicine; Estados Unidos
Fil: Koonin, Eugene V.. National Center For Biotechnology Information ; Estados Unidos
Fil: Scorrano, Luca. Università di Padova; Italia
Fil: Pellegrini, Luca. Laval University; Canadá
description Contacts between organelles create microdomains that play major roles in regulating key intracellular activities and signaling pathways, but whether they also regulate systemic functions remains unknown. Here, we report the ultrastructural organization and dynamics of the inter-organellar contact established by sheets of curved rough endoplasmic reticulum closely wrapped around the mitochondria (wrappER). To elucidate the in vivo function of this contact, mouse liver fractions enriched in wrappER-associated mitochondria are analyzed by transcriptomics, proteomics, and lipidomics. The biochemical signature of the wrappER points to a role in the biogenesis of very-low-density lipoproteins (VLDL). Altering wrappER-mitochondria contacts curtails VLDL secretion and increases hepatic fatty acids, lipid droplets, and neutral lipid content. Conversely, acute liver-specific ablation of Mttp, the most upstream regulator of VLDL biogenesis, recapitulates this hepatic dyslipidemia phenotype and promotes remodeling of the wrappER-mitochondria contact. The discovery that liver wrappER-mitochondria contacts participate in VLDL biology suggests an involvement of inter-organelle contacts in systemic lipid homeostasis.
publishDate 2021
dc.date.none.fl_str_mv 2021-03
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/11336/173327
Anastasia, Irene; Ilacqua, Nicolò; Raimondi, Andrea; Lemieux, Philippe; Ghandehari-Alavijeh, Rana; et al.; Mitochondria-rough-ER contacts in the liver regulate systemic lipid homeostasis; Cell Press; Cell Reports; 34; 11; 3-2021; 1-29
2211-1247
CONICET Digital
CONICET
url http://hdl.handle.net/11336/173327
identifier_str_mv Anastasia, Irene; Ilacqua, Nicolò; Raimondi, Andrea; Lemieux, Philippe; Ghandehari-Alavijeh, Rana; et al.; Mitochondria-rough-ER contacts in the liver regulate systemic lipid homeostasis; Cell Press; Cell Reports; 34; 11; 3-2021; 1-29
2211-1247
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.cell.com/cell-reports/fulltext/S2211-1247(21)00187-X
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2021.108873
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Cell Press
publisher.none.fl_str_mv Cell Press
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
_version_ 1842268661548580864
score 13.13397

Publicaciones similares