A p300 and SIRT1 Regulated Acetylation Switch of C/EBPα Controls Mitochondrial Function

Mohamad A Zaini, Christine Müller, Tristan V de Jong, Tobias Ackermann, Götz Hartleben, Gertrud Kortman, Karl-Heinz Gührs, Fabrizia Fusetti, Oliver H Krämer, Victor Guryev, Cornelis F Calkhoven

OnderzoeksoutputAcademicpeer review

30 Citaten (Scopus)
362 Downloads (Pure)


Cellular metabolism is a tightly controlled process in which the cell adapts fluxes through metabolic pathways in response to changes in nutrient supply. Among the transcription factors that regulate gene expression and thereby cause changes in cellular metabolism is the basic leucine-zipper (bZIP) transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα). Protein lysine acetylation is a key post-translational modification (PTM) that integrates cellular metabolic cues with other physiological processes. Here, we show that C/EBPα is acetylated by the lysine acetyl transferase (KAT) p300 and deacetylated by the lysine deacetylase (KDAC) sirtuin1 (SIRT1). SIRT1 is activated in times of energy demand by high levels of nicotinamide adenine dinucleotide (NAD+) and controls mitochondrial biogenesis and function. A hypoacetylated mutant of C/EBPα induces the transcription of mitochondrial genes and results in increased mitochondrial respiration. Our study identifies C/EBPα as a key mediator of SIRT1-controlled adaption of energy homeostasis to changes in nutrient supply.

Originele taal-2English
Pagina's (van-tot)497-511
Aantal pagina's15
TijdschriftCell reports
Nummer van het tijdschrift2
StatusPublished - 9-jan.-2018

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