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

dc.creatorAnastasia, Irene
dc.creatorIlacqua, Nicolò
dc.creatorRaimondi, Andrea
dc.creatorLemieux, Philippe
dc.creatorGhandehari-Alavijeh, Rana
dc.creatorFaure, Guilhem
dc.creatorMekhedov, Sergei L.
dc.creatorWilliams, Kevin J.
dc.creatorCaicci, Federico
dc.creatorValle, Giorgio
dc.creatorGiacomello, Marta
dc.creatorQuiroga, Ariel Dario
dc.creatorLehner, Richard
dc.creatorMiksis, Michael J.
dc.creatorToth, Katalin
dc.creatorde Aguiar Vallim, Thomas Q.
dc.creatorKoonin, Eugene V.
dc.creatorScorrano, Luca
dc.creatorPellegrini, Luca
dc.date2021-03
dc.date.accessioned2023-08-31T00:27:50Z
dc.date.available2023-08-31T00:27:50Z
dc.identifierhttp://hdl.handle.net/11336/173327
dc.identifierAnastasia, 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
dc.identifier2211-1247
dc.identifierCONICET Digital
dc.identifierCONICET
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8543448
dc.descriptionContacts 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.
dc.descriptionFil: Anastasia, Irene. Laval University; Canadá. Brain Research Center; Canadá
dc.descriptionFil: Ilacqua, Nicolò. Laval University; Canadá. Brain Research Center; Canadá
dc.descriptionFil: Raimondi, Andrea. San Raffaele Scientific Institute; Italia
dc.descriptionFil: Lemieux, Philippe. Brain Research Center; Canadá
dc.descriptionFil: Ghandehari-Alavijeh, Rana. Brain Research Center; Canadá
dc.descriptionFil: Faure, Guilhem. Broad Institute of MIT and Harvard; Estados Unidos. National Center For Biotechnology Information; Estados Unidos
dc.descriptionFil: Mekhedov, Sergei L.. National Center For Biotechnology Information ; Estados Unidos
dc.descriptionFil: Williams, Kevin J.. University of California at Los Angeles. School of Medicine; Estados Unidos
dc.descriptionFil: Caicci, Federico. Università di Padova; Italia
dc.descriptionFil: Valle, Giorgio. Università di Padova; Italia
dc.descriptionFil: Giacomello, Marta. Università di Padova; Italia
dc.descriptionFil: 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
dc.descriptionFil: Lehner, Richard. University of Alberta; Canadá
dc.descriptionFil: Miksis, Michael J.. Northwestern University; Estados Unidos
dc.descriptionFil: Toth, Katalin. University of Ottawa; Canadá
dc.descriptionFil: de Aguiar Vallim, Thomas Q.. University of California at Los Angeles. School of Medicine; Estados Unidos
dc.descriptionFil: Koonin, Eugene V.. National Center For Biotechnology Information ; Estados Unidos
dc.descriptionFil: Scorrano, Luca. Università di Padova; Italia
dc.descriptionFil: Pellegrini, Luca. Laval University; Canadá
dc.formatapplication/pdf
dc.formatapplication/pdf
dc.languageeng
dc.publisherCell Press
dc.relationinfo:eu-repo/semantics/altIdentifier/url/https://www.cell.com/cell-reports/fulltext/S2211-1247(21)00187-X
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2021.108873
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subjectENDOPLASMIC RETICULUM
dc.subjectINTER-ORGANELLE CONTACT
dc.subjectLIPOPROTEIN
dc.subjectLIVER METABOLISM
dc.subjectMAM
dc.subjectMITOCHONDRIA
dc.subjectMUP
dc.subjectRRBP1
dc.subjectVLDL
dc.subjectWRAPPER
dc.subjecthttps://purl.org/becyt/ford/3.1
dc.subjecthttps://purl.org/becyt/ford/3
dc.titleMitochondria-rough-ER contacts in the liver regulate systemic lipid homeostasis
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:ar-repo/semantics/artículo
dc.typeinfo:eu-repo/semantics/publishedVersion


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