title: Acetyl-coenzyme A: a metabolic master regulator of autophagy and longevity.
abstract: As the major lysosomal degradation pathway, autophagy represents the guardian of cellular homeostasis, removing damaged and potentially harmful material and replenishing energy reserves in conditions of starvation. Given its vast physiological importance, autophagy is crucially involved in the process of aging and associated pathologies. Although the regulation of autophagy strongly depends on nutrient availability, specific metabolites that modulate autophagic responses are poorly described. Recently, we revealed nucleo-cytosolic acetyl-coenzyme A (AcCoA) as a phylogenetically conserved inhibitor of starvation-induced and age-associated autophagy. AcCoA is the sole acetyl-group donor for protein acetylation, explaining why pharmacological or genetic manipulations that modify the concentrations of nucleo-cytosolic AcCoA directly affect the levels of protein acetylation. The acetylation of histones and cytosolic proteins inversely correlates with the rate of autophagy in yeast and mammalian cells, respectively, despite the fact that the routes of de novo AcCoA synthesis differ across phyla. Thus, we propose nucleo-cytosolic AcCoA to act as a conserved metabolic rheostat, linking the cellular metabolic state to the regulation of autophagy via effects on protein acetylation.
authors.affiliation: Institute of Molecular Biosciences; University of Graz; Graz, Austria.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Schroeder
authors.affiliation: Institute of Molecular Biosciences; University of Graz; Graz, Austria.
authors.forename: Tobias
authors.initials: T
authors.lastname: Pendl
authors.affiliation: Institute of Molecular Biosciences; University of Graz; Graz, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Zimmermann
authors.affiliation: Institute of Molecular Biosciences; University of Graz; Graz, Austria.
authors.forename: Tobias
authors.initials: T
authors.lastname: Eisenberg
authors.affiliation: Institute of Molecular Biosciences; University of Graz; Graz, Austria.
authors.forename: Didac
authors.initials: D
authors.lastname: Carmona-Gutierrez
authors.affiliation: Institute of Molecular Biosciences; University of Graz; Graz, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Ruckenstuhl
authors.affiliation: INSERM U848; Pavillon de Recherche 1; Villejuif, France; Metabolomics and Cell Biology Platforms; Institut Gustave Roussy; Pavillon de Recherche 1; Villejuif, France; Université Paris Sud; Faculté de Médecine; Le Kremlin Bicêtre; France.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Mariño
authors.affiliation: INSERM U848; Pavillon de Recherche 1; Villejuif, France; Metabolomics and Cell Biology Platforms; Institut Gustave Roussy; Pavillon de Recherche 1; Villejuif, France; Université Paris Sud; Faculté de Médecine; Le Kremlin Bicêtre; France.
authors.forename: Federico
authors.initials: F
authors.lastname: Pietrocola
authors.affiliation: Institute of Molecular Biosciences; University of Graz; Graz, Austria; Division of Endocrinology and Metabolism; Dept. of Internal Medicine; Medical University of Graz; Graz, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Harger
authors.affiliation: HEALTH-Institute for Biomedicine and Health Sciences; Joanneum Research Forschungsgesellschaft m.b.H.; Graz, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Magnes
authors.affiliation: Division of Endocrinology and Metabolism; Dept. of Internal Medicine; Medical University of Graz; Graz, Austria; HEALTH-Institute for Biomedicine and Health Sciences; Joanneum Research Forschungsgesellschaft m.b.H.; Graz, Austria.
authors.forename: Frank
authors.initials: F
authors.lastname: Sinner
authors.affiliation: Division of Endocrinology and Metabolism; Dept. of Internal Medicine; Medical University of Graz; Graz, Austria; HEALTH-Institute for Biomedicine and Health Sciences; Joanneum Research Forschungsgesellschaft m.b.H.; Graz, Austria.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Pieber
authors.affiliation: Department of Dermatology; University Freiburg Medical Center; Freiburg, Germany.
authors.forename: Jörn
authors.initials: J
authors.lastname: Dengjel
authors.affiliation: Institute for Biology/Genetics; Freie Universität; Berlin, Germany; NeuroCure; Charité; Berlin, Germany.
authors.forename: Stephan J
authors.initials: SJ
authors.lastname: Sigrist
authors.affiliation: INSERM U848; Pavillon de Recherche 1; Villejuif, France; Metabolomics and Cell Biology Platforms; Institut Gustave Roussy; Pavillon de Recherche 1; Villejuif, France; Université Paris Sud; Faculté de Médecine; Le Kremlin Bicêtre; France; Equipe 11 labellisée Ligue contre le cancer; INSERM U1138; Centre de Recherche des Cordeliers; Paris, France; Pôle de Biologie; Hôpital Européen Georges Pompidou; AP-HP; Paris, France; Université Paris Descartes; Sorbonne Paris Cité; Paris, France.
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
authors.affiliation: Institute of Molecular Biosciences; University of Graz; Graz, Austria.
authors.forename: Frank
authors.initials: F
authors.lastname: Madeo
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism*; D000818:Animals; D001343:Autophagy; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D008136:Longevity; D053858:Metabolic Networks and Pathways; D051379:Mice; D008954:Models, Biological; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism
chemical_list: D000105:Acetyl Coenzyme A
keywords: ATG; acetyl-coenzyme A; aging; autophagy; epigenetics; histone acetylation; transcription