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Concept

Sirtuin

Related publications (28)

Revealing chromatin-specific functions of histone deacylases

Beat Fierz, Carlos Moreno Yruela

Histone deacylases are erasers of Nε-acyl-lysine post-translational modifications and have been targeted for decades for the treatment of cancer, neurodegeneration and other disorders. Due to their relatively promiscuous activity on peptide substrates in v ...

2024

Anti-miR-873-5p improves alcohol-related liver disease by enhancing hepatic deacetylation via SIRT1

Kristina Schoonjans

Background & Aims: Current therapies for the treatment of alcohol-related liver disease (ALD) have proven largely ineffective. Patients relapse and the disease progresses even after liver transplantation. Altered epigenetic mechanisms are characteristic of ...

Elsevier2024

Substrates and Cyclic Peptide Inhibitors of the Oligonucleotide-Activated Sirtuin 7

Alexander Lund Nielsen

The sirtuins are NAD+-dependent lysine deacylases, comprising seven isoforms (SIRT1-7) in humans, which are involved in the regulation of a plethora of biological processes, including gene expression and metabolism. The sirtuins share a common hydrolytic m ...

Wiley-VCH Verlag GmbH2023

SIRT7 suppresses energy expenditure and thermogenesis by regulating brown adipose tissue functions in mice

Johan Auwerx

Brown adipose tissue plays a central role in the regulation of the energy balance by expending energy to produce heat. NAD(+)-dependent deacylase sirtuins have widely been recognized as positive regulators of brown adipose tissue thermogenesis. However, he ...

Nature Portfolio2022

The role of nicotinamide riboside metabolism in pancreatic beta cells

Angélique Satoko Cercillieux

Pancreatic beta cells play a major role in the regulation of glucose homeostasis by secreting insulin in response to elevated blood glucose levels. A gradual deterioration of functional beta cell mass and the chronic elevation of blood glucose levels are c ...

EPFL2022

Pharmacological and genetic perturbation establish SIRT5 as a promising target in breast cancer

Johan Auwerx, Bo Li

SIRT5 is a member of the sirtuin family of NAD(+)-dependent protein lysine deacylases implicated in a variety of physiological processes. SIRT5 removes negatively charged malonyl, succinyl, and glutaryl groups from lysine residues and thereby regulates mul ...

SPRINGERNATURE2021

Mitochondrial Deacetylase Sirt3 Reduces Vascular Dysfunction and Hypertension While Sirt3 Depletion in Essential Hypertension Is Linked to Vascular Inflammation and Oxidative Stress

Johan Auwerx

Rationale: Hypertension represents a major risk factor for stroke, myocardial infarction, and heart failure and affects 30% of the adult population. Mitochondrial dysfunction contributes to hypertension, but specific mechanisms are unclear. The mitochondri ...

2020

NAD(+) homeostasis in health and disease

Johan Auwerx, Elena Katsyuba, Mario Romani, Dina Hofer

The conceptual evolution of nicotinamide adenine dinucleotide (NAD(+)) from being seen as a simple metabolic cofactor to a pivotal cosubstrate for proteins regulating metabolism and longevity, including the sirtuin family of protein deacylases, has led to ...

2020

Niacin: an old lipid drug in a new NAD(+) dress

Johan Auwerx, Elena Katsyuba, Mario Romani, Dina Hofer

Niacin, the first antidyslipidemic drug, has been at the center stage of lipid research for many decades before the discovery of statins. However, to date, despite its remarkable effects on lipid profiles, the clinical outcomes of niacin treatment on cardi ...

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC2019

Nuclear receptor corepressor 1 represses cardiac hypertrophy

Johan Auwerx, Chao Li, Jun Wang, Yan Liu

The function of nuclear receptor corepressor 1 (NCoR1) in cardiomyocytes is unclear, and its physiological and pathological implications are unknown. Here, we found that cardiomyocyte-specific NCoR1 knockout (CMNKO) mice manifested cardiac hypertrophy at b ...

2019

De novo NAD(+) synthesis enhances mitochondrial function and improves health

Johan Auwerx, Kristina Schoonjans, Dongryeol Ryu, Adrienne Joëlle Laurence Mottis, Elena Katsyuba, Karim Laurent Gariani, Olli Juhani Matilainen, Marika Olga Zietak

Nicotinamide adenine dinucleotide (NAD(+)) is a co-substrate for several enzymes, including the sirtuin family of NAD(+)-dependent protein deacylases. Beneficial effects of increased NAD(+) levels and sirtuin activation on mitochondrial homeostasis, organi ...

NATURE PUBLISHING GROUP2018

Lysine acetylation stoichiometry and proteomics analyses reveal pathways regulated by sirtuin 1 in human cells

Diego Chiappe

Lysine acetylation is a widespread posttranslational modification affecting many biological pathways. Recent studies indicate that acetylated lysine residues mainly exhibit low acetylation occupancy, but challenges in sample preparation and analysis make i ...

Amer Soc Biochemistry Molecular Biology Inc2017

Modulating NAD(+) metabolism, from bench to bedside

Johan Auwerx, Elena Katsyuba

Discovered in the beginning of the 20(th) century, nicotinamide adenine dinucleotide (NAD(+)) has evolved from a simple oxidoreductase cofactor to being an essential cosubstrate for a wide range of regulatory proteins that include the sirtuin family of NAD ...

Wiley2017

Role of ACMSD in regulation of NAD+ metabolism and mitochondrial function

Elena Katsyuba

Discovered in the beginning of the 20th century, nicotinamide adenine dinucleotide (NAD+) has evolved from a simple oxidoreductase cofactor to being an essential cosubstrate for a wide range of regulatory proteins that include most notoriously the sirtuin ...

EPFL2017

Circadian and Feeding Rhythms Orchestrate the Diurnal Liver Acetylome

Felix Naef, Carlos Canto Alvarez, Frédéric Bruno Martin Gachon, Loïc Dayon, Daniel Alain Dominique Marie Mauvoisin, Joanna Ratajczak, Jingkui Wang

Lysine acetylation is involved in various biological processes and is considered a key reversible post-translational modification in the regulation of gene expression, enzyme activity, and subcellular localization. This post-translational modification is t ...

Elsevier2017

Mitochondrial Post-translational Modifications and Metabolic Control: Sirtuins and Beyond

Carlos Canto Alvarez

Introduction: In order to maintain metabolic homeostasis, organisms adjust the capacity and efficiency of ATP generation to changes in energetic demand and supply. While the transcriptional control of mitochondrial biogenesis allows to adapt mitochondrial ...

Bentham Science Publ Ltd2017

Inhibiting poly ADP-ribosylation increases fatty acid oxidation and protects against fatty liver disease

Johan Auwerx, Jun Yong Kim, Kristina Schoonjans, Alessia Perino, Dongryeol Ryu, Elena Katsyuba, Hongbo Zhang, Keir Joe Menzies, Pooja Jha, Karim Laurent Gariani, Vera Monica Lemos Da Silva

Background & Aims: To date, no pharmacological therapy has been approved for non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to evaluate the therapeutic potential of poly ADP-ribose polymerase (PARP) inhibitors in mouse models o ...

Elsevier Science Bv2017

The role of nicotinamide riboside kinases in mammalian NAD⁺ metabolism

Joanna Ratajczak

NAD+ has emerged as a central metabolic node and an important co-substrate for the activity of various enzymes, including the protein deacetylase SIRT1. Different strategies to increase NAD+ bioavailability have been shown to boost SIRT1 activity, which re ...

EPFL2017

SIRT2-and NRF2-Targeting Thiazole-Containing Compound with Therapeutic Activity in Huntington's Disease Models

There are currently no disease-modifying therapies for the neurodegenerative disorder Huntington's disease (HD). This study identified novel thiazole-containing inhibitors of the deacetylase sirtuin-2 (SIRT2) with neuroprotective activity in ex vivo brain ...

Cell Press2016

Dietary restriction and Sirtuin 1 in metabolic health: connections and divergences

Carlos Canto Alvarez

Aging is the major risk factor for a constellation of multifactorial diseases, including insulin resistance, diabetes and cardiovascular complications. Dietary restriction has been shown to delay or prevent the manifestation of age-related health decline, ...

Cambridge Univ Press2016