Circadian and Feeding Rhythms Orchestrate the Diurnal Liver Acetylome

Aug 17, 2017Cell reports

Daily liver protein changes controlled by body clock and eating patterns

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Abstract

A comprehensive acetylome map of the mouse liver reveals rhythmic acetylation patterns that are correlated with subcellular localization and metabolic pathways.

Rhythmic acetylated proteins display specific phases based on their subcellular localization.
These rhythmic acetylation patterns correlate with related metabolites in regulated pathways.
Mitochondrial proteins are notably over-represented among the rhythmically acetylated proteins.
SIRT3-dependent deacetylation is highly correlated with these mitochondrial proteins.
NAD levels, which influence SIRT3 activity, are regulated by both feeding rhythms and the circadian clock.
The diurnal acetylome is dependent on a functional circadian clock, impacting key metabolic pathways in the mouse liver.

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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 NADis orchestrated by both feeding rhythms and the circadian clock through the NADsalvage 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. + + +

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Circadian and Feeding Rhythms Orchestrate the Diurnal Liver Acetylome

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