Mitochondrial O-GlcNAc Transferase Interacts ...
Type de document :
Article dans une revue scientifique: Article original
DOI :
URL permanente :
Titre :
Mitochondrial O-GlcNAc Transferase Interacts with and Modifies Many Proteins and Its Up-Regulation Affects Mitochondrial Function and Cellular Energy Homeostasis
Auteur(s) :
Jóźwiak, Paweł [Auteur]
University of Lódź = Uniwersytet Łódzki
Ciesielski, Piotr [Auteur]
University of Lódź = Uniwersytet Łódzki
Zakrzewski, Piotr K. [Auteur]
University of Lódź = Uniwersytet Łódzki
Kozal, Karolina [Auteur]
University of Lódź = Uniwersytet Łódzki
Oracz, Joanna [Auteur]
Łódź University of Technology
Budryn, Grażyna [Auteur]
Łódź University of Technology
Żyżelewicz, Dorota [Auteur]
Łódź University of Technology
Flament, Stéphanie [Auteur]
Institut Michel Eugène Chevreul - FR 2638 [IMEC]
Edouart (vercoutter), Anne-Sophie [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Bray, Fabrice [Auteur]
Institut Michel Eugène Chevreul - FR 2638 [IMEC]
Lefebvre, Tony [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Krześlak, Anna [Auteur]
University of Lódź = Uniwersytet Łódzki
University of Lódź = Uniwersytet Łódzki
Ciesielski, Piotr [Auteur]
University of Lódź = Uniwersytet Łódzki
Zakrzewski, Piotr K. [Auteur]
University of Lódź = Uniwersytet Łódzki
Kozal, Karolina [Auteur]
University of Lódź = Uniwersytet Łódzki
Oracz, Joanna [Auteur]
Łódź University of Technology
Budryn, Grażyna [Auteur]
Łódź University of Technology
Żyżelewicz, Dorota [Auteur]
Łódź University of Technology
Flament, Stéphanie [Auteur]
Institut Michel Eugène Chevreul - FR 2638 [IMEC]
Edouart (vercoutter), Anne-Sophie [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Bray, Fabrice [Auteur]
Institut Michel Eugène Chevreul - FR 2638 [IMEC]
Lefebvre, Tony [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Krześlak, Anna [Auteur]
University of Lódź = Uniwersytet Łódzki
Titre de la revue :
Cancers
Numéro :
13
Pagination :
2956
Éditeur :
MDPI AG
Date de publication :
2021-06-12
ISSN :
2072-6694
Mot(s)-clé(s) en anglais :
mOGT
O-GlcNAc
mitochondria
glucose
energy metabolism
breast cancer
O-GlcNAc
mitochondria
glucose
energy metabolism
breast cancer
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Chimie/Chimie théorique et/ou physique
Chimie/Chimie théorique et/ou physique
Résumé en anglais : [en]
O-GlcNAcylation is a cell glucose sensor. The addition of O-GlcNAc moieties to target protein is catalyzed by the O-Linked N-acetylglucosamine transferase (OGT). OGT is encoded by a single gene that yields differentially ...
Lire la suite >O-GlcNAcylation is a cell glucose sensor. The addition of O-GlcNAc moieties to target protein is catalyzed by the O-Linked N-acetylglucosamine transferase (OGT). OGT is encoded by a single gene that yields differentially spliced OGT isoforms. One of them is targeted to mitochondria (mOGT). Although the impact of O-GlcNAcylation on cancer cells biology is well documented, mOGT’s role remains poorly investigated. We performed studies using breast cancer cells with up-regulated mOGT or its catalytic inactive mutant to identify proteins specifically modified by mOGT. Proteomic approaches included isolation of mOGT protein partners and O-GlcNAcylated proteins from mitochondria-enriched fraction followed by their analysis by mass spectrometry. Moreover, we analyzed the impact of mOGT dysregulation on mitochondrial activity and cellular metabolism using a variety of biochemical assays. We found that mitochondrial OGT expression is glucose-dependent. Elevated mOGT expression affected the mitochondrial transmembrane potential and increased intramitochondrial ROS generation. Moreover, mOGT up-regulation caused a decrease in cellular ATP level. We identified many mitochondrial proteins as mOGT substrates. Most of these proteins are localized in the mitochondrial matrix and the inner mitochondrial membrane and participate in mitochondrial respiration, fatty acid metabolism, transport, translation, apoptosis, and mtDNA processes. Our findings suggest that mOGT interacts with and modifies many mitochondrial proteins, and its dysregulation affects cellular bioenergetics and mitochondria function.Lire moins >
Lire la suite >O-GlcNAcylation is a cell glucose sensor. The addition of O-GlcNAc moieties to target protein is catalyzed by the O-Linked N-acetylglucosamine transferase (OGT). OGT is encoded by a single gene that yields differentially spliced OGT isoforms. One of them is targeted to mitochondria (mOGT). Although the impact of O-GlcNAcylation on cancer cells biology is well documented, mOGT’s role remains poorly investigated. We performed studies using breast cancer cells with up-regulated mOGT or its catalytic inactive mutant to identify proteins specifically modified by mOGT. Proteomic approaches included isolation of mOGT protein partners and O-GlcNAcylated proteins from mitochondria-enriched fraction followed by their analysis by mass spectrometry. Moreover, we analyzed the impact of mOGT dysregulation on mitochondrial activity and cellular metabolism using a variety of biochemical assays. We found that mitochondrial OGT expression is glucose-dependent. Elevated mOGT expression affected the mitochondrial transmembrane potential and increased intramitochondrial ROS generation. Moreover, mOGT up-regulation caused a decrease in cellular ATP level. We identified many mitochondrial proteins as mOGT substrates. Most of these proteins are localized in the mitochondrial matrix and the inner mitochondrial membrane and participate in mitochondrial respiration, fatty acid metabolism, transport, translation, apoptosis, and mtDNA processes. Our findings suggest that mOGT interacts with and modifies many mitochondrial proteins, and its dysregulation affects cellular bioenergetics and mitochondria function.Lire moins >
Langue :
Anglais
Comité de lecture :
Oui
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
Université de Lille
CNRS
CNRS
Équipe(s) de recherche :
O-GlcNAcylation, signalisation cellulaire et cycle cellulaire
Date de dépôt :
2021-06-21T13:03:34Z
2021-06-23T14:54:43Z
2021-06-23T14:54:43Z
Fichiers
- P21.05 Jozwiak et al., 2021 Cancers.pdf
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