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Reversible acetylation of PGC-1: connecting energy sensors and effectors to guarantee metabolic flexibility

Oncogene volume 29, pages 4617–4624 (2010)Cite this article

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Abstract

Organisms adapt their metabolism to meet ever changing environmental conditions. This metabolic adaptation involves at a cellular level the fine tuning of mitochondrial function, which is mainly under the control of the transcriptional co-activator proliferator-activated receptor γ co-activator (PGC)-1α. Changes in PGC-1α activity coordinate a transcriptional response, which boosts mitochondrial activity in times of energy needs and attenuates it when energy demands are low. Reversible acetylation has emerged as a key way to alter PGC-1α activity. Although it is well established that PGC-1α is deacetylated and activated by Sirt1 and acetylated and inhibited by GCN5, less is known regarding how these enzymes themselves are regulated. Recently, it became clear that the energy sensor, AMP-activated kinase (AMPK) translates the effects of energy stress into altered Sirt1 activity by regulating the intracellular level of its co-substrate nicotinamide adenine dinucleotide (NAD)+. Conversely, the enzyme ATP citrate lyase (ACL), relates energy balance to GCN5, through the control of the nuclear production of acetyl-CoA, the substrate for GCN5's acetyltransferase activity. We review here how these metabolic signaling pathways, affecting GCN5 and Sirt1 activity, allow the reversible acetylation–deacetylation of PGC-1α and the adaptation of mitochondrial energy homeostasis to energy levels.

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Acknowledgements

This work was supported by grants from the Ecole Polytechnique Fédérale de Lausanne, Swiss National Science Foundation, NIH (DK59820) and the European Research Council Ideas programme (Sirtuins; ERC-2008-AdG23118).

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  1. Ecole Polytechnique Fédérale de Lausanne (EPFL), Laboratory of Integrative and Systems Physiology, Lausanne, Switzerland

    E H Jeninga, K Schoonjans & J Auwerx

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Jeninga, E., Schoonjans, K. & Auwerx, J. Reversible acetylation of PGC-1: connecting energy sensors and effectors to guarantee metabolic flexibility. Oncogene 29, 4617–4624 (2010). https://doi.org/10.1038/onc.2010.206

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