Protein acetylation in metabolism - metabolites and cofactors.
Reversible acetylation was initially described as an epigenetic mechanism regulating DNA accessibility. Since then, this process has emerged as a controller of histone and nonhistone acetylation that integrates key physiological processes such as metabolism, circadian rhythm and cell cycle, along with gene regulation in various organisms. The widespread and reversible nature of acetylation also revitalized interest in the mechanisms that regulate lysine acetyltransferases (KATs) and deacetylases (KDACs) in health and disease. Changes in protein or histone acetylation are especially relevant for many common diseases including obesity, diabetes mellitus, neurodegenerative diseases and cancer, as well as for some rare diseases such as mitochondrial diseases and lipodystrophies. In this Review, we examine the role of reversible acetylation in metabolic control and how changes in levels of metabolites or cofactors, including nicotinamide adenine dinucleotide, nicotinamide, coenzyme A, acetyl coenzyme A, zinc and butyrate and/or β-hydroxybutyrate, directly alter KAT or KDAC activity to link energy status to adaptive cellular and organismal homeostasis.
Interdisciplinary School of Health Sciences, University of Ottawa, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada.
Keir J
KJ
Menzies
Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne, Station 15, 1015 Lausanne, Switzerland.
Hongbo
H
Zhang
Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne, Station 15, 1015 Lausanne, Switzerland.
Elena
E
Katsyuba
Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne, Station 15, 1015 Lausanne, Switzerland.
Johan
J
Auwerx
D020155:3-Hydroxybutyric Acid / Q000378:metabolism; D000107:Acetylation; D000818:Animals; D003067:Coenzymes / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D044127:Epigenesis, Genetic / Q000502:physiology; D051548:Histone Acetyltransferases / Q000378:metabolism; D006801:Humans; D009536:Niacinamide / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000502:physiology*
D003067:Coenzymes; D009536:Niacinamide; D051548:Histone Acetyltransferases; D020155:3-Hydroxybutyric Acid