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- Title
Reversible acetylation of PGC-1: connecting energy sensors and effectors to guarantee metabolic flexibility.
- Authors
Jeninga, E H; Schoonjans, K; Auwerx, J
- 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.
- Subjects
MITOCHONDRIA; HOMEOSTASIS; ACETYLATION; NAD (Coenzyme); METABOLISM
- Publication
Oncogene, 2010, Vol 29, Issue 33, p4617
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/onc.2010.206