Circadian and Feeding Rhythms Orchestrate the Diurnal Liver Acetylome

Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Daniel Mauvoisin, Florian Atger, Loïc Dayon, Antonio Núñez Galindo, Jingkui Wang, Eva Martin, Laetitia Da Silva, Ivan Montoliu, Sebastiano Collino, Francois-Pierre Martin, Joanna Ratajczak, Carles Cantó, Martin Kussmann, Felix Naef, Frédéric Gachon
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.

Graphical abstract

Teaser

Mauvoisin et al. provide a rhythmic acetylome map of the mouse liver. Rhythmic acetylated proteins showed subcellular localization-specific phases with an over-representation of SIRT3 targets. Feeding rhythms and the circadian clock regulate NAD⁺ synthesis through the salvage and nicotinamide riboside pathways, affecting metabolite accumulation.


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