Identification of VAT1 as a regulator of lipid metabolism at mitochondria endoplasmic reticulum contact sites and implications in liver pathology

[eng] Lipid homeostasis is of vital importance for cellular health and its disruption is a hallmark of disease. Recently, our lab reported that ablation of Mitofusin 2 (MFN2) leads to liver disease, a phenotype driven by deficient phosphatidylserine (PS) transport at the mitochondria- endoplasmic re...

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Detalles Bibliográficos
Autor: Danezi, Aikaterini
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/221216
Acceso en línea:https://hdl.handle.net/2445/221216
http://hdl.handle.net/10803/694505
Access Level:acceso abierto
Palabra clave:Citologia
Àcids grassos
Metabolisme dels lípids
Fetge
Cytology
Fatty acids
Lipid metabolism
Liver
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spelling Identification of VAT1 as a regulator of lipid metabolism at mitochondria endoplasmic reticulum contact sites and implications in liver pathologyDanezi, AikateriniCitologiaÀcids grassosMetabolisme dels lípidsFetgeCytologyFatty acidsLipid metabolismLiver[eng] Lipid homeostasis is of vital importance for cellular health and its disruption is a hallmark of disease. Recently, our lab reported that ablation of Mitofusin 2 (MFN2) leads to liver disease, a phenotype driven by deficient phosphatidylserine (PS) transport at the mitochondria- endoplasmic reticulum (ER) contact sites (MERCs). Despite the capacity of MFN2 to extract PS from membranes and generate PS-rich domains, evidence suggested that it does not possess lipid transport properties. In this study, we propose that Vesicle amine transport protein 1 (VAT1) localises at MERCs, interacts with MFN2 and its PS transport capacity is modulated by MFN2 in vitro. Our results in cells additionally suggest a functional relationship between VAT1 and MFN2. Finally, our study reveals that ablation of hepatic VAT1 in mice leads to sex-dependent metabolic adaptations and has a detrimental effect on the lipid profile of mitochondria-associated membranes, ER and pure mitochondria.[cat] L'homeòstasi lipídica és de vital importància per a la salut cel·lular i la seva interrupció és un segell distintiu de la malaltia. Recentment, el nostre laboratori va reportar que l'ablació de la mitofusina 2 (MFN2) condueix a una malaltia hepàtica, un fenotip impulsat pel transport deficient de fosfatidilserina (PS) als llocs de contacte mitocondri-reticle endoplasmàtic (ER) (MERC). Malgrat la capacitat de MFN2 per extreure PS de les membranes i generar dominis rics en PS, l'evidència experimental suggereix que no posseeix propietats de transport de lípids. En aquest estudi, proposem que la proteïna de transport d'amina de vesícula 1 (VAT1) localitza als MERC, interacciona amb MFN2 i la seva capacitat de transport de PS està modulada per MFN2 in vitro. Els nostres resultats en cèl·lules suggereixen, a més, una relació funcional entre VAT1 i MFN2. Finalment, el nostre estudi revela que l'ablació de VAT1 hepàtic en ratolins condueix a adaptacions metabòliques dependents del sexe i té un efecte perjudicial sobre el perfil lipídic de les membranes associades a mitocondris, ER i mitocondris purs.Universitat de BarcelonaZorzano Olarte, AntonioUniversitat de Barcelona. Departament de Bioquímica i Biomedicina Molecular2025info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/221216http://hdl.handle.net/10803/694505Tesis Doctorals - Departament - Bioquímica i Biomedicina Molecularreponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglés(c) Danezi, Aikaterini, 2025info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2212162026-05-27T06:46:51Z
dc.title.none.fl_str_mv Identification of VAT1 as a regulator of lipid metabolism at mitochondria endoplasmic reticulum contact sites and implications in liver pathology
title Identification of VAT1 as a regulator of lipid metabolism at mitochondria endoplasmic reticulum contact sites and implications in liver pathology
spellingShingle Identification of VAT1 as a regulator of lipid metabolism at mitochondria endoplasmic reticulum contact sites and implications in liver pathology
Danezi, Aikaterini
Citologia
Àcids grassos
Metabolisme dels lípids
Fetge
Cytology
Fatty acids
Lipid metabolism
Liver
title_short Identification of VAT1 as a regulator of lipid metabolism at mitochondria endoplasmic reticulum contact sites and implications in liver pathology
title_full Identification of VAT1 as a regulator of lipid metabolism at mitochondria endoplasmic reticulum contact sites and implications in liver pathology
title_fullStr Identification of VAT1 as a regulator of lipid metabolism at mitochondria endoplasmic reticulum contact sites and implications in liver pathology
title_full_unstemmed Identification of VAT1 as a regulator of lipid metabolism at mitochondria endoplasmic reticulum contact sites and implications in liver pathology
title_sort Identification of VAT1 as a regulator of lipid metabolism at mitochondria endoplasmic reticulum contact sites and implications in liver pathology
dc.creator.none.fl_str_mv Danezi, Aikaterini
author Danezi, Aikaterini
author_facet Danezi, Aikaterini
author_role author
dc.contributor.none.fl_str_mv Zorzano Olarte, Antonio
Universitat de Barcelona. Departament de Bioquímica i Biomedicina Molecular
dc.subject.none.fl_str_mv Citologia
Àcids grassos
Metabolisme dels lípids
Fetge
Cytology
Fatty acids
Lipid metabolism
Liver
topic Citologia
Àcids grassos
Metabolisme dels lípids
Fetge
Cytology
Fatty acids
Lipid metabolism
Liver
description [eng] Lipid homeostasis is of vital importance for cellular health and its disruption is a hallmark of disease. Recently, our lab reported that ablation of Mitofusin 2 (MFN2) leads to liver disease, a phenotype driven by deficient phosphatidylserine (PS) transport at the mitochondria- endoplasmic reticulum (ER) contact sites (MERCs). Despite the capacity of MFN2 to extract PS from membranes and generate PS-rich domains, evidence suggested that it does not possess lipid transport properties. In this study, we propose that Vesicle amine transport protein 1 (VAT1) localises at MERCs, interacts with MFN2 and its PS transport capacity is modulated by MFN2 in vitro. Our results in cells additionally suggest a functional relationship between VAT1 and MFN2. Finally, our study reveals that ablation of hepatic VAT1 in mice leads to sex-dependent metabolic adaptations and has a detrimental effect on the lipid profile of mitochondria-associated membranes, ER and pure mitochondria.
publishDate 2025
dc.date.none.fl_str_mv 2025
dc.type.none.fl_str_mv info:eu-repo/semantics/doctoralThesis
info:eu-repo/semantics/publishedVersion
format doctoralThesis
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/221216
http://hdl.handle.net/10803/694505
url https://hdl.handle.net/2445/221216
http://hdl.handle.net/10803/694505
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv (c) Danezi, Aikaterini, 2025
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Danezi, Aikaterini, 2025
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universitat de Barcelona
publisher.none.fl_str_mv Universitat de Barcelona
dc.source.none.fl_str_mv Tesis Doctorals - Departament - Bioquímica i Biomedicina Molecular
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.81155

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