Neddylation of phosphoenolpyruvate carboxykinase 1 controls glucose metabolism.

Autor:	Gonzalez-Rellan MJ; Department of Physiology, CIMUS, University of Santiago de Compostela, Instituto de Investigación Sanitaria, Santiago de Compostela, Spain; CIBER Fisiopatologia de la Obesidad y Nutrición (CIBERobn), Madrid, Spain., Fernández U; Department of Physiology, CIMUS, University of Santiago de Compostela, Instituto de Investigación Sanitaria, Santiago de Compostela, Spain; CIBER Fisiopatologia de la Obesidad y Nutrición (CIBERobn), Madrid, Spain., Parracho T; Department of Physiology, CIMUS, University of Santiago de Compostela, Instituto de Investigación Sanitaria, Santiago de Compostela, Spain; CIBER Fisiopatologia de la Obesidad y Nutrición (CIBERobn), Madrid, Spain., Novoa E; Department of Physiology, CIMUS, University of Santiago de Compostela, Instituto de Investigación Sanitaria, Santiago de Compostela, Spain; CIBER Fisiopatologia de la Obesidad y Nutrición (CIBERobn), Madrid, Spain., Fondevila MF; Department of Physiology, CIMUS, University of Santiago de Compostela, Instituto de Investigación Sanitaria, Santiago de Compostela, Spain; CIBER Fisiopatologia de la Obesidad y Nutrición (CIBERobn), Madrid, Spain., da Silva Lima N; Department of Physiology, CIMUS, University of Santiago de Compostela, Instituto de Investigación Sanitaria, Santiago de Compostela, Spain; CIBER Fisiopatologia de la Obesidad y Nutrición (CIBERobn), Madrid, Spain., Ramos L; Department of Biochemistry, CIMUS, Instituto de Investigación Sanitaria, Santiago de Compostela, Spain., Rodríguez A; CIBER Fisiopatologia de la Obesidad y Nutrición (CIBERobn), Madrid, Spain; Department of Endocrinology & Nutrition, Metabolic Research Laboratory, Clínica Universidad de Navarra, University of Navarra, IdiSNA, Pamplona, Navarra, Spain., Serrano-Maciá M; Liver Disease Lab, BRTA CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Derio, Bizkaia, Spain., Perez-Mejias G; Instituto de Investigaciones Químicas (IIQ), Centro de Investigaciones Científicas Isla de la Cartuja (cicCartuja), Universidad de Sevilla-CSIC. Avda. Americo Vespucio 49, 41092 Sevilla, Spain., Chantada-Vazquez P; Proteomic Unit, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela 15705, A Coruña, Spain., Riobello C; Gene Regulatory Control in Disease, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain., Veyrat-Durebex C; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Diabetes Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland., Tovar S; Department of Physiology, CIMUS, University of Santiago de Compostela, Instituto de Investigación Sanitaria, Santiago de Compostela, Spain; CIBER Fisiopatologia de la Obesidad y Nutrición (CIBERobn), Madrid, Spain., Coppari R; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Diabetes Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland., Woodhoo A; Gene Regulatory Control in Disease, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain; Galician Agency of Innovation (GAIN), Xunta de Galicia, Santiago de Compostela, Spain., Schwaninger M; University of Lübeck, Institute for Experimental and Clinical Pharmacology and Toxicology, Lübeck, Germany., Prevot V; University of Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, UMR-S 1172, European Genomic Institute for Diabetes (EGID), 59000 Lille, France., Delgado TC; Liver Disease Lab, BRTA CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Derio, Bizkaia, Spain., Lopez M; Department of Physiology, CIMUS, University of Santiago de Compostela, Instituto de Investigación Sanitaria, Santiago de Compostela, Spain; CIBER Fisiopatologia de la Obesidad y Nutrición (CIBERobn), Madrid, Spain., Diaz-Quintana A; Instituto de Investigaciones Químicas (IIQ), Centro de Investigaciones Científicas Isla de la Cartuja (cicCartuja), Universidad de Sevilla-CSIC. Avda. Americo Vespucio 49, 41092 Sevilla, Spain., Dieguez C; Department of Physiology, CIMUS, University of Santiago de Compostela, Instituto de Investigación Sanitaria, Santiago de Compostela, Spain; CIBER Fisiopatologia de la Obesidad y Nutrición (CIBERobn), Madrid, Spain., Guallar D; Department of Biochemistry, CIMUS, Instituto de Investigación Sanitaria, Santiago de Compostela, Spain., Frühbeck G; CIBER Fisiopatologia de la Obesidad y Nutrición (CIBERobn), Madrid, Spain; Department of Endocrinology & Nutrition, Metabolic Research Laboratory, Clínica Universidad de Navarra, University of Navarra, IdiSNA, Pamplona, Navarra, Spain., Diaz-Moreno I; Instituto de Investigaciones Químicas (IIQ), Centro de Investigaciones Científicas Isla de la Cartuja (cicCartuja), Universidad de Sevilla-CSIC. Avda. Americo Vespucio 49, 41092 Sevilla, Spain., Bravo SB; Proteomic Unit, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela 15705, A Coruña, Spain., Martinez-Chantar ML; Liver Disease Lab, BRTA CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Derio, Bizkaia, Spain. Electronic address: mlmartinez@cicbiogune.es., Nogueiras R; Department of Physiology, CIMUS, University of Santiago de Compostela, Instituto de Investigación Sanitaria, Santiago de Compostela, Spain; CIBER Fisiopatologia de la Obesidad y Nutrición (CIBERobn), Madrid, Spain; Galician Agency of Innovation (GAIN), Xunta de Galicia, Santiago de Compostela, Spain. Electronic address: ruben.nogueiras@usc.es.
Jazyk:	angličtina
Zdroj:	Cell metabolism [Cell Metab] 2023 Sep 05; Vol. 35 (9), pp. 1630-1645.e5. Date of Electronic Publication: 2023 Aug 03.
DOI:	10.1016/j.cmet.2023.07.003
Abstrakt:	Neddylation is a post-translational mechanism that adds a ubiquitin-like protein, namely neural precursor cell expressed developmentally downregulated protein 8 (NEDD8). Here, we show that neddylation in mouse liver is modulated by nutrient availability. Inhibition of neddylation in mouse liver reduces gluconeogenic capacity and the hyperglycemic actions of counter-regulatory hormones. Furthermore, people with type 2 diabetes display elevated hepatic neddylation levels. Mechanistically, fasting or caloric restriction of mice leads to neddylation of phosphoenolpyruvate carboxykinase 1 (PCK1) at three lysine residues-K278, K342, and K387. We find that mutating the three PCK1 lysines that are neddylated reduces their gluconeogenic activity rate. Molecular dynamics simulations show that neddylation of PCK1 could re-position two loops surrounding the catalytic center into an open configuration, rendering the catalytic center more accessible. Our study reveals that neddylation of PCK1 provides a finely tuned mechanism of controlling glucose metabolism by linking whole nutrient availability to metabolic homeostasis. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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