title: Circadian acetylome reveals regulation of mitochondrial metabolic pathways.
abstract: The circadian clock is constituted by a complex molecular network that integrates a number of regulatory cues needed to maintain organismal homeostasis. To this effect, posttranslational modifications of clock proteins modulate circadian rhythms and are thought to convert physiological signals into changes in protein regulatory function. To explore reversible lysine acetylation that is dependent on the clock, we have characterized the circadian acetylome in WT and Clock-deficient (Clock(-/-)) mouse liver by quantitative mass spectrometry. Our analysis revealed that a number of mitochondrial proteins involved in metabolic pathways are heavily influenced by clock-driven acetylation. Pathways such as glycolysis/gluconeogenesis, citric acid cycle, amino acid metabolism, and fatty acid metabolism were found to be highly enriched hits. The significant number of metabolic pathways whose protein acetylation profile is altered in Clock(-/-) mice prompted us to link the acetylome to the circadian metabolome previously characterized in our laboratory. Changes in enzyme acetylation over the circadian cycle and the link to metabolite levels are discussed, revealing biological implications connecting the circadian clock to cellular metabolic state.
authors: Center for Epigenetics and Metabolism, Department of Biological Chemistry, University of California, Irvine, CA 92697, USA.
authors: Selma
authors: S
authors: Masri
authors: Vishal R
authors: VR
authors: Patel
authors: Kristin L
authors: KL
authors: Eckel-Mahan
authors: Shahaf
authors: S
authors: Peleg
authors: Ignasi
authors: I
authors: Forne
authors: Andreas G
authors: AG
authors: Ladurner
authors: Pierre
authors: P
authors: Baldi
authors: Axel
authors: A
authors: Imhof
authors: Paolo
authors: P
authors: Sassone-Corsi
mesh_terms: D000107:Acetylation; D000818:Animals; D056926:CLOCK Proteins / Q000172:deficiency / Q000378:metabolism; D002940:Circadian Rhythm / Q000235:genetics; D016000:Cluster Analysis; D008239:Lysine / Q000378:metabolism; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D055442:Metabolome / Q000235:genetics; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D020543:Proteome / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics
chemical_list: D010455:Peptides; D020543:Proteome; D056926:CLOCK Proteins; C538944:Clock protein, mouse; D008239:Lysine