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Mitochondrial O-GlcNAc Transferase Interacts with and Modifies Many Proteins and Its Up-Regulation Affects Mitochondrial Function and Cellular Energy Homeostasis.
Józwiak, Pawel; Ciesielski, Piotr; Zakrzewski, Piotr K; Kozal, Karolina; Oracz, Joanna; Budryn, Grazyna; Zyzelewicz, Dorota; Flament, Stéphanie; Vercoutter-Edouart, Anne-Sophie; Bray, Fabrice; Lefebvre, Tony; Krzeslak, Anna.
Afiliação
  • Józwiak P; Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland.
  • Ciesielski P; Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland.
  • Zakrzewski PK; Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland.
  • Kozal K; Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland.
  • Oracz J; Institute of Food Technology and Analysis, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, 90-924 Lodz, Poland.
  • Budryn G; Institute of Food Technology and Analysis, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, 90-924 Lodz, Poland.
  • Zyzelewicz D; Institute of Food Technology and Analysis, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, 90-924 Lodz, Poland.
  • Flament S; Institut Eugène-Michel Chevreul, CNRS, MSAP USR 3290, FR 3688 FRABIO, FR 2638, Université de Lille, 59000 Lille, France.
  • Vercoutter-Edouart AS; Unité de Glycobiologie Structurale et Fonctionnelle, CNRS, UMR 8576, UGSF, Université de Lille, 59000 Lille, France.
  • Bray F; Institut Eugène-Michel Chevreul, CNRS, MSAP USR 3290, FR 3688 FRABIO, FR 2638, Université de Lille, 59000 Lille, France.
  • Lefebvre T; Unité de Glycobiologie Structurale et Fonctionnelle, CNRS, UMR 8576, UGSF, Université de Lille, 59000 Lille, France.
  • Krzeslak A; Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland.
Cancers (Basel) ; 13(12)2021 Jun 12.
Article em En | MEDLINE | ID: mdl-34204801
ABSTRACT
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2021 Tipo de documento: Article