Regulation of Glycolytic Enzyme Phosphoglycerate Mutase-1 by Sirt1 Protein-mediated Deacetylation

Hallows, William C.; Yu, Wei; Denu, John M.

doi:10.1074/jbc.m111.317404

Cited by 158 publications

(125 citation statements)

References 44 publications

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“…5C). PGM, another glycolytic enzyme, is also known to be regulated by acetylation (8). Cardiac PGM acetylation markedly increased in 21-day-old compared with 1-day and 7-day-old rabbits, whereas protein expression of PGM was decreased following birth (Fig.…”

Section: Resultsmentioning

confidence: 97%

Acetylation and succinylation contribute to maturational alterations in energy metabolism in the newborn heart

Fukushima

Alrob

Zhang

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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Fukushima A, Alrob OA, Zhang L, Wagg CS, Altamimi T, Rawat S, Rebeyka IM, Kantor PF, Lopaschuk GD. Acetylation and succinylation contribute to maturational alterations in energy metabolism in the newborn heart. Am J Physiol Heart Circ Physiol 311: H347-H363, 2016. First published June 3, 2016; doi:10.1152/ajpheart.00900.2015.-Dramatic maturational changes in cardiac energy metabolism occur in the newborn period, with a shift from glycolysis to fatty acid oxidation. Acetylation and succinylation of lysyl residues are novel posttranslational modifications involved in the control of cardiac energy metabolism. We investigated the impact of changes in protein acetylation/succinylation on the maturational changes in energy metabolism of 1-, 7-, and 21-day-old rabbit hearts. Cardiac fatty acid ␤-oxidation rates increased in 21-day vs. 1-and 7-day-old hearts, whereas glycolysis and glucose oxidation rates decreased in 21-day-old hearts. The fatty acid oxidation enzymes, long-chain acyl-CoA dehydrogenase (LCAD) and ␤-hydroxyacylCoA dehydrogenase (␤-HAD), were hyperacetylated with maturation, positively correlated with their activities and fatty acid ␤-oxidation rates. This alteration was associated with increased expression of the mitochondrial acetyltransferase, general control of amino acid synthesis 5 like 1 (GCN5L1), since silencing GCN5L1 mRNA in H9c2 cells significantly reduced acetylation and activity of LCAD and ␤-HAD. An increase in mitochondrial ATP production rates with maturation was associated with the decreased acetylation of peroxisome proliferator-activated receptor-␥ coactivator-1␣, a transcriptional regulator for mitochondrial biogenesis. In addition, hypoxiainducible factor-1␣, hexokinase, and phosphoglycerate mutase expression declined postbirth, whereas acetylation of these glycolytic enzymes increased. Phosphorylation rather than acetylation of pyruvate dehydrogenase (PDH) increased in 21-day-old hearts, accounting for the low glucose oxidation postbirth. A maturational increase was also observed in succinylation of PDH and LCAD. Collectively, our data are the first suggesting that acetylation and succinylation of the key metabolic enzymes in newborn hearts play a crucial role in cardiac energy metabolism with maturation.Listen to this article's corresponding podcast at http://ajpheart.podbean. com/e/acetylation-control-of-energy-metabolism-in-newborn-hearts/. myocardial fatty acid oxidation; lysine acetylation; lysine succinylation; newborn heart NEW & NOTEWORTHYThe present study is the first showing that alterations in acetylation and succinylation control of metabolic enzymes contribute to the dramatic shift in cardiac energy metabolism from glycolysis to fatty acid ␤-oxidation seen during maturation. Our results suggest that lysine acetylation enhances cardiac fatty acid ␤-oxidation and inhibits glycolysis during maturation.OVER 1% OF NEWBORNS ARE DIAGNOSED with congenital heart disease (CHD), with one-third of these needing surgery within the first months of life (36). Despite the major advance...

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Section: Resultsmentioning

confidence: 97%

Acetylation and succinylation contribute to maturational alterations in energy metabolism in the newborn heart

Fukushima

Alrob

Zhang

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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“…All these examples represent inhibitory effects of acetylation. Thus far, no examples of bacterial acetylation-stimulating enzymatic activity have been discovered, but such regulation has been described in eukaryotes (94,95).…”

Section: Functional Consequences Of Protein Acetylationmentioning

confidence: 99%

Regulation, Function, and Detection of Protein Acetylation in Bacteria

2017

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N -Lysine acetylation is now recognized as an abundant posttranslational modification (PTM) that influences many essential biological pathways. Advancements in mass spectrometry-based proteomics have led to the discovery that bacteria contain hundreds of acetylated proteins, contrary to the prior notion of acetylation events being rare in bacteria. Although the mechanisms that regulate protein acetylation are still not fully defined, it is understood that this modification is finely tuned via both enzymatic and nonenzymatic mechanisms. The opposing actions of Gcn5-related N-acetyltransferases (GNATs) and deacetylases, including sirtuins, provide the enzymatic control of lysine acetylation. A nonenzymatic mechanism of acetylation has also been demonstrated and proven to be prominent in bacteria, as well as in mitochondria. The functional consequences of the vast majority of the identified acetylation sites remain unknown. From studies in mammalian systems, acetylation of critical lysine residues was shown to impact protein function by altering its structure, subcellular localization, and interactions. It is becoming apparent that the same diversity of functions can be found in bacteria. Here, we review current knowledge of the mechanisms and the functional consequences of acetylation in bacteria. Additionally, we discuss the methods available for detecting acetylation sites, including quantitative mass spectrometry-based methods, which promise to promote this field of research. We conclude with possible future directions and broader implications of the study of protein acetylation in bacteria.

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“…In this regard, SIRT1 activity is tightly linked to AMP kinase (AMPK) (Feige et al 2008;Fulco et al 2008), since AMPK drives expression of the NAD synthetic enzyme NAMPT (Canto et al 2009(Canto et al , 2010, and SIRT1 deacetylates and activates the AMPK activator kinase LKB1 (Hou et al 2008;Lan et al 2008). At the same time, SIRT1 turns down glycolytic metabolism by deacetylating glycolytic enzymes (Hallows et al 2012) and one of their key transcriptional inducers, HIF-1a (Lim et al 2010). One must assume that repressing HIF-1a is especially important, since SIRT3 and SIRT6 also target this pathway.…”

Section: Cellular Effectsmentioning

confidence: 99%

Calorie restriction and sirtuins revisited

2013

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Calorie or dietary restriction (CR) has attracted attention because it is the oldest and most robust way to extend rodent life span. The idea that the nutrient sensors, termed sirtuins, might mediate effects of CR was proposed 13 years ago and has been challenged in the intervening years. This review addresses these challenges and draws from a great body of new data in the sirtuin field that shows a systematic redirection of mammalian physiology in response to diet by sirtuins. The prospects for drugs that can deliver at least a subset of the benefits of CR seems very real.

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Regulation of Glycolytic Enzyme Phosphoglycerate Mutase-1 by Sirt1 Protein-mediated Deacetylation

Abstract: Background: Recent proteomic studies suggest that lysine acetylation might regulate many metabolic pathways. Results: NAD ϩ -dependent deacetylase Sirt1 deacetylates phosphoglycerate mutase-1 (PGAM1) and attenuates catalytic

Cited by 158 publications

References 44 publications

Acetylation and succinylation contribute to maturational alterations in energy metabolism in the newborn heart

Acetylation and succinylation contribute to maturational alterations in energy metabolism in the newborn heart

Regulation, Function, and Detection of Protein Acetylation in Bacteria

Calorie restriction and sirtuins revisited

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