Emerging Roles of SIRT5 in Metabolism, Cancer, and SARS-CoV-2 Infection DOI Creative Commons
Emanuele Fabbrizi, Francesco Fiorentino, Vincenzo Carafa

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(6), P. 852 - 852

Published: March 9, 2023

Sirtuin 5 (SIRT5) is a predominantly mitochondrial enzyme catalyzing the removal of glutaryl, succinyl, malonyl, and acetyl groups from lysine residues through NAD+-dependent deacylase mechanism. SIRT5 an important regulator cellular homeostasis modulates activity proteins involved in different metabolic pathways such as glycolysis, tricarboxylic acid (TCA) cycle, fatty oxidation, electron transport chain, generation ketone bodies, nitrogenous waste management, reactive oxygen species (ROS) detoxification. controls wide range aspects myocardial energy metabolism plays critical roles heart physiology stress responses. Moreover, has protective function context neurodegenerative diseases, while it acts context-dependent tumor promoter or suppressor. In addition, current research demonstrated that implicated SARS-CoV-2 infection, although opposing conclusions have been drawn studies. Here, we review knowledge on molecular actions under both healthy diseased settings, well its functional effects targets. Finally, revise potential therapeutic target provide overview currently reported modulators, which include activators inhibitors.

Language: Английский

From Krebs to clinic: glutamine metabolism to cancer therapy DOI
Brian J. Altman,

Zachary E. Stine,

Chi V. Dang

et al.

Nature reviews. Cancer, Journal Year: 2016, Volume and Issue: 16(10), P. 619 - 634

Published: July 29, 2016

Language: Английский

Citations

1813
Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials DOI Creative Commons
Yuan Cheng, He Cai, Manni Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2019, Volume and Issue: 4(1)

Published: Dec. 17, 2019

Epigenetic alternations concern heritable yet reversible changes in histone or DNA modifications that regulate gene activity beyond the underlying sequence. dysregulation is often linked to human disease, notably cancer. With development of various drugs targeting epigenetic regulators, epigenetic-targeted therapy has been applied treatment hematological malignancies and exhibited viable therapeutic potential for solid tumors preclinical clinical trials. In this review, we summarize aberrant functions enzymes methylation, acetylation methylation during tumor progression highlight inhibitors targeted at enzymes.

Language: Английский

Citations

900
The Role of Sirtuins in Antioxidant and Redox Signaling DOI Open Access
Chandra K. Singh, Gagan Chhabra, Mary A. Ndiaye

et al.

Antioxidants and Redox Signaling, Journal Year: 2017, Volume and Issue: 28(8), P. 643 - 661

Published: Sept. 11, 2017

Antioxidant and redox signaling (ARS) events are regulated by critical molecules that modulate antioxidants, reactive oxygen species (ROS) or nitrogen (RNS), and/or oxidative stress within the cell. Imbalances in these can disturb cellular functions to become pathogenic. Sirtuins serve as important regulators of ARS cells. Recent Advances: (SIRTs 1-7) a family nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases with ability deacetylate nonhistone targets. studies show sirtuins regulation variety processes associated ARS. SIRT1, SIRT3, SIRT5 protect cell from ROS, SIRT2, SIRT6, SIRT7 key genes mechanisms. Interestingly, SIRT4 has been shown induce ROS production antioxidative roles well.A complete understanding homeostasis is very understand normal functioning well pathological manifestations. In this review, we have provided discussion on role We also discussed mechanistic interactions among different sirtuins. Indeed, sirtuin biology could be at multiple fronts.Sirtuins emerging mammalian physiology stress-mediated situations. Studies needed dissect mechanisms maintaining homeostasis. Efforts required assess targetability management redox-regulated diseases. Antioxid. Redox Signal. 28, 643-661.

Language: Английский

Citations

676
The multifaceted functions of sirtuins in cancer DOI

Angeliki Chalkiadaki,

Leonard Guarente

Nature reviews. Cancer, Journal Year: 2015, Volume and Issue: 15(10), P. 608 - 624

Published: Sept. 18, 2015

Language: Английский

Citations

450
Sirtuin functions and modulation: from chemistry to the clinic DOI Creative Commons
Vincenzo Carafa, Dante Rotili, Mariantonietta Forgione

et al.

Clinical Epigenetics, Journal Year: 2016, Volume and Issue: 8(1)

Published: May 24, 2016

Sirtuins are NAD+-dependent histone deacetylases regulating important metabolic pathways in prokaryotes and eukaryotes involved many biological processes such as cell survival, senescence, proliferation, apoptosis, DNA repair, metabolism, caloric restriction. The seven members of this family enzymes considered potential targets for the treatment human pathologies including neurodegenerative diseases, cardiovascular cancer. Furthermore, recent interest focusing on sirtuin modulators epigenetic players regulation fundamental has prompted increased efforts to discover new small molecules able modify activity. Here, we review role, mechanism action, function sirtuins, well their inhibitors activators.

Language: Английский

Citations

348
Functions of the sirtuin deacylase SIRT5 in normal physiology and pathobiology DOI
Surinder Kumar, David B. Lombard

Critical Reviews in Biochemistry and Molecular Biology, Journal Year: 2018, Volume and Issue: 53(3), P. 311 - 334

Published: April 11, 2018

Sirtuins are NAD+-dependent protein deacylases/ADP-ribosyltransferases that have emerged as candidate targets for new therapeutics to treat metabolic disorders and other diseases, including cancer. The sirtuin SIRT5 resides primarily in the mitochondrial matrix catalyzes removal of negatively charged lysine acyl modifications; succinyl, malonyl, glutaryl groups. Evidence has now accumulated document roles a significant regulator cellular homeostasis, context- cell-type specific manner, been observed previously family members. regulates substrates involved glycolysis, TCA cycle, fatty acid oxidation, electron transport chain, ketone body formation, nitrogenous waste management, ROS detoxification, among processes. plays pivotal cardiac physiology stress responses is regulation numerous aspects myocardial energy metabolism. implicated neoplasia, both tumor promoter suppressor context-specific may serve protective function setting neurodegenerative disorders. Here, we review current understanding functional impacts on its targets, molecular functions normal pathological conditions. Finally, will discuss potential utility drug target also summarize status, progress, challenges developing small molecule compounds modulate activity with high potency specificity.

Language: Английский

Citations

220
NADP+-IDH Mutations Promote Hypersuccinylation that Impairs Mitochondria Respiration and Induces Apoptosis Resistance DOI Creative Commons
Li Feng,

Xiadi He,

Dingwei Ye

et al.

Molecular Cell, Journal Year: 2015, Volume and Issue: 60(4), P. 661 - 675

Published: Nov. 1, 2015

Language: Английский

Citations

205
SHMT2 Desuccinylation by SIRT5 Drives Cancer Cell Proliferation DOI
Xin Yang, Zhe Wang, Xin Li

et al.

Cancer Research, Journal Year: 2017, Volume and Issue: 78(2), P. 372 - 386

Published: Nov. 27, 2017

The mitochondrial serine hydroxymethyltransferase SHMT2, which catalyzes the rate-limiting step in catabolism, drives cancer cell proliferation, but how this role is regulated undefined. Here, we report that sirtuin SIRT5 desuccinylates SHMT2 to increase its activity and drive catabolism tumor cells. interaction directly mediated desuccinylation of lysine 280 on was crucial for activating enzymatic activity. Conversely, hypersuccinylation at sufficient inhibit downregulate growth vitro vivo Notably, inactivation led downregulation abrogated under metabolic stress. Our results reveal a pivotal signal cells adapt processes rapid growth, they highlight as candidate target suppressing strategy block growth.Significance: These findings novel mechanism controlling proliferation by blocking general impede growth. Cancer Res; 78(2); 372-86. ©2017 AACR.

Language: Английский

Citations

195
Dual Tumor Suppressor and Tumor Promoter Action of Sirtuins in Determining Malignant Phenotype DOI Creative Commons
Vincenzo Carafa, Lucia Altucci, Angela Nebbioso

et al.

Frontiers in Pharmacology, Journal Year: 2019, Volume and Issue: 10

Published: Jan. 29, 2019

Sirtuins, class III histone deacetylases, are differentially expressed in several human cancers, where they display both oncogenic and tumor-suppressive properties depending on cellular context experimental conditions. Sirtuins involved many important biological processes play a critical role cancer initiation, promotion progression. A growing body of evidence indicates the involvement sirtuins regulating three tumor processes: epithelial-to-mesenchymal transition (EMT), invasion metastasis. Many responsible for metabolic reprogramming drug resistance by inactivating cell death pathways promoting uncontrolled proliferation. In this review, we summarize current knowledge discuss their puzzling dual function as suppressors promoters, future development novel tailored sirtuin-based therapies.

Language: Английский

Citations

155
The ins and outs of serine and glycine metabolism in cancer DOI
Shauni Lien Geeraerts, Elien Heylen, Kim De Keersmaecker

et al.

Nature Metabolism, Journal Year: 2021, Volume and Issue: 3(2), P. 131 - 141

Published: Jan. 28, 2021

Language: Английский

Citations

152