A New Frontier in Studying Dietary Phytochemicals in Cancer and in Health: Metabolic and Epigenetic Reprogramming DOI Creative Commons
Ahmad Shannar, Md Shahid Sarwar, Ah‐Ng Tony Kong

et al.

Preventive Nutrition and Food Science, Journal Year: 2022, Volume and Issue: 27(4), P. 335 - 346

Published: Dec. 31, 2022

Metabolic rewiring and epigenetic reprogramming are closely inter-related, mutually regulate each other to control cell growth in cancer initiation, promotion, progression, metastasis.Epigenetics plays a crucial role regulating normal cellular functions as well pathological conditions many diseases, including cancer.Conversely, certain mitochondrial metabolites considered essential cofactors regulators of mechanisms.Furthermore, dysregulation metabolism promotes tumor reprograms the cells produce bioenergy needed support proliferation.Hence, metabolic which alters metabolites/epigenetic cofactors, would drive landscape, DNA methylation histone modification, that could lead progression.Recognizing diverse array benefits phytochemicals, they gaining increasing interest interception treatment.One significant mechanisms treatment by phytochemicals is key pathways remodeling epigenetics.This review focuses on epigenetics investigates potential can mitigate cancer.

Language: Английский

Coenzyme A biosynthesis: mechanisms of regulation, function and disease DOI
Samuel A. Barritt, Sarah DuBois-Coyne, Christian C. Dibble

et al.

Nature Metabolism, Journal Year: 2024, Volume and Issue: 6(6), P. 1008 - 1023

Published: June 13, 2024

Language: Английский

Citations

18
Chiral Posttranslational Modification to Lysine ε-Amino Groups DOI
Carlos Moreno–Yruela, Michael Bæk, Fabrizio Monda

et al.

Accounts of Chemical Research, Journal Year: 2022, Volume and Issue: 55(10), P. 1456 - 1466

Published: May 2, 2022

The sophistication of proteomic analysis has revealed that protein lysine residues are posttranslationally modified by a variety acyl groups. Protein acetylation regulates metabolism, gene expression, and microtubule formation been extensively studied; however, the understanding biological significance other posttranslational modifications (PTMs) is still in its infancy. acylation mediated either acyltransferase "writer" enzymes or nonenzymatic mechanisms hydrolase enzymes, termed "erasers", cleave various PTMs to reverse state. We have studied human deacylase comprising 11 Zn2+-dependent histone deacetylases (HDACs) 7 NAD+-consuming sirtuins (SIRTs), over past decade. thus developed selective inhibitors molecular probes substrate scope each enzyme using chemically synthesized peptide substrates photo-cross-linking probes. Recently, we turned our attention containing stereogenic center, such as ε-N-β-hydroxybutyryllysine (Kbhb) ε-N-lactyllysine (Kla), comprise pair mirror image stereoisomers modifications. Both found on histones, where they affect transcription response specific metabolic states, cytosolic mitochondrial involved fatty acid oxidation glycolysis respectively. Thus, chiral side chains give rise two distinct diastereomeric products, with separate origins potentially different activities exhibited writer eraser enzymes. Lysine l-lactylation originates from l-lactate, major energy carrier produced pyruvate after glycolysis, it highly induced states Warburg effect. l-Lactate can possibly be activated acyl-coenzyme A (CoA) synthetases transferred acetyltransferases p300. d-Lactylation, hand, arises primarily reaction d-lactylglutathione, an intermediate glyoxalase pathway. In addition their origin, both K(l-la) K(d-la) erased HDACs catalytic efficiencies. Also, K(l-bhb) K(d-bhb) arise metabolites but depend interconnected pathways, ε-N-3-hydroxy-3-methylglutaryllysine (Khmg) originate single precursor may then regulated differently Distinguishing between individual therefore crucial importance. present Account, will (1) revisit long-standing evidence for production dynamics enantiomeric forms serve ε-N-acyllysine (2) highlight outstanding questions recent literature resulting these metabolites.

Language: Английский

Citations

42
A global view of the human post-translational modification landscape DOI Creative Commons
Naoya Kitamura, James J. Galligan

Biochemical Journal, Journal Year: 2023, Volume and Issue: 480(16), P. 1241 - 1265

Published: Aug. 23, 2023

Post-translational modifications (PTMs) provide a rapid response to stimuli, finely tuning metabolism and gene expression maintain homeostasis. Advances in mass spectrometry over the past two decades have significantly expanded list of known PTMs biology as instrumentation continues improve, this will surely grow. While many been studied detail (e.g. phosphorylation, acetylation), vast majority lack defined mechanisms for their regulation impact on cell fate. In review, we highlight field PTM research it currently stands, discussing that dictate site specificity, analytical methods detection study, chemical tools can be leveraged define regulation. addition, approaches needed discover validate novel PTMs. Lastly, review starting point those interested biology, providing comprehensive what is regarding metabolic origins.

Language: Английский

Citations

35
HDAC1/2/3 are major histone desuccinylases critical for promoter desuccinylation DOI Creative Commons
Jialun Li, Lu Lu, Lingling Liu

et al.

Cell Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: Aug. 15, 2023

Lysine succinylation is one of the major post-translational modifications occurring on histones and believed to have significant roles in regulating chromatin structure function. Currently, histone desuccinylation widely be catalyzed by members SIRT family deacetylases. Here, we report that fact primarily class I HDAC1/2/3. Inhibition or depletion HDAC1/2/3 resulted a marked increase global succinylation, whereas ectopic expression but not their deacetylase inactive mutants downregulated succinylation. We demonstrated complexes robust desuccinylase activity vitro. Genomic landscape analysis revealed highly enriched at gene promoters inhibition HDAC results elevation promoter Furthermore, our integrated positively correlates with transcriptional activity. Collectively, demonstrate proteins are desuccinylases particularly important for desuccinylation. Our study thus sheds new light role regulation.

Language: Английский

Citations

30
Mechanisms of metabolism-coupled protein modifications DOI
Bingsen Zhang, Frank C. Schroeder

Nature Chemical Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

Language: Английский

Citations

1
Divergent roles for propionate and butyrate in colorectal cancer epigenetics DOI Creative Commons
Yuen Jian Cheong, Sophie Trefely

Nature Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

Language: Английский

Citations

1
Metabolism-driven chromatin dynamics: Molecular principles and technological advances DOI
Varun Sahu, Chao Lü

Molecular Cell, Journal Year: 2025, Volume and Issue: 85(2), P. 262 - 275

Published: Jan. 1, 2025

Language: Английский

Citations

1
A genetically encoded fluorescent biosensor for visualization of acetyl-CoA in live cells DOI
Joseph J. Smith, Taylor R. Valentino,

Austin H. Ablicki

et al.

Cell chemical biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

1
PARylated PDHE1α generates acetyl-CoA for local chromatin acetylation and DNA damage repair DOI
Jun Zhang, Feng Chen, Yuan Tian

et al.

Nature Structural & Molecular Biology, Journal Year: 2023, Volume and Issue: 30(11), P. 1719 - 1734

Published: Sept. 21, 2023

Language: Английский

Citations

22
The emerging importance of the α-keto acid dehydrogenase complexes in serving as intracellular and intercellular signaling platforms for the regulation of metabolism DOI Creative Commons
Ryan J. Mailloux

Redox Biology, Journal Year: 2024, Volume and Issue: 72, P. 103155 - 103155

Published: April 10, 2024

The α-keto acid dehydrogenase complex (KDHc) class of mitochondrial enzymes is composed four members: pyruvate (PDHc), α-ketoglutarate (KGDHc), branched-chain keto (BCKDHc), and 2-oxoadipate (OADHc). These enzyme complexes occupy critical metabolic intersections that connect monosaccharide, amino acid, fatty metabolism to Krebs cycle flux oxidative phosphorylation (OxPhos). This feature also imbues KDHc with the heightened capacity serve as platforms for propagation intracellular intercellular signaling. a source sink hydrogen peroxide (mtH2O2), vital second messenger used trigger eustress pathways. Notably, deactivation through reversible oxidation by mtH2O2 other electrophiles modulates availability several intermediates related metabolites which powerful messengers. play important roles in modulation epigenetic programming nucleus provision various acyl-CoAs, are acylate proteinaceous lysine residues. nucleosomal control acylation achieved PDHc KGDHc localization nuclear lumen. In this review, I discuss emerging concepts signaling fulfilled complexes. highlight their function serving redox sensors how can be cells regulate required cell Coupled this, describe detail defects cause disease states disruption homeodynamics deregulation Finally, propose functions controlled modification vicinal lipoic thiols E2 subunit

Language: Английский

Citations

7