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Cell Rep ; 20(7): 1729-1743, 2017 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-28813682

RESUMO

Lysine acetylation is involved in various biological processes and is considered a key reversible post-translational modification in the regulation of gene expression, enzyme activity, and subcellular localization. This post-translational modification is therefore highly relevant in the context of circadian biology, but its characterization on the proteome-wide scale and its circadian clock dependence are still poorly described. Here, we provide a comprehensive and rhythmic acetylome map of the mouse liver. Rhythmic acetylated proteins showed subcellular localization-specific phases that correlated with the related metabolites in the regulated pathways. Mitochondrial proteins were over-represented among the rhythmically acetylated proteins and were highly correlated with SIRT3-dependent deacetylation. SIRT3 activity being nicotinamide adenine dinucleotide (NAD)+ level-dependent, we show that NAD+ is orchestrated by both feeding rhythms and the circadian clock through the NAD+ salvage pathway but also via the nicotinamide riboside pathway. Hence, the diurnal acetylome relies on a functional circadian clock and affects important diurnal metabolic pathways in the mouse liver.


Assuntos
Relógios Circadianos/fisiologia , Ritmo Circadiano/fisiologia , Fígado/enzimologia , Proteínas Mitocondriais/metabolismo , Processamento de Proteína Pós-Traducional , Proteoma/metabolismo , Fatores de Transcrição ARNTL/deficiência , Fatores de Transcrição ARNTL/genética , Acetilação , Animais , Criptocromos/deficiência , Criptocromos/genética , Ingestão de Alimentos/fisiologia , Lisina , Redes e Vias Metabólicas/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Mitocondriais/genética , NAD/metabolismo , Fotoperíodo , Proteoma/genética , Sirtuína 3/genética , Sirtuína 3/metabolismo
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