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

/, Papers/A p300 and SIRT1 Regulated Acetylation Switch of C/EBPa Controls Mitochondrial Function

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

Cell Press  | 9 januari 2018 |

Summary

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/EBPa). Protein lysine acetylation is a key post-translational modification (PTM) that integrates cellular metabolic cues with other  physiological processes. Here, we show that C/EBPa 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/EBPa induces the transcription of mitochondrial genes and results in increased mitochondrial respiration. Our study identifies C/EBPa as a key mediator of SIRT1-controlled adaption of energy homeostasis to changes in nutrient supply.

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Auteurs

Mohamad A. Zaini,1,2 Christine Müller,1 Tristan V. de Jong,1 Tobias Ackermann,1 Götz Hartleben,1 Gertrud Kortman,1 Karl-Heinz Gührs,2 Fabrizia Fusetti,3 Oliver H. Krämer,4 Victor Guryev,1 and Cornelis F. Calkhoven1,5,*

Affiliaties

1 European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands

2 Leibniz Institute on Aging, Fritz Lipmann Institute, 07745 Jena, Germany

3 Department of Biochemistry, Netherlands Proteomics Centre, Groningen Biological Sciences and Biotechnology Institute, University of bGroningen, 9747 AG Groningen, the Netherlands

4 Institute of Toxicology, University Medical Center Mainz, 55131 Mainz, Germany

5 Lead Contact

*Correspondence: c.f.calkhoven@umcg.nl

2018-01-22T10:08:27+00:00