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Johan Auwerx

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Related publications (283)

Direct supplementation with Urolithin A overcomes limitations of dietary exposure and gut microbiome variability in healthy adults to achieve consistent levels across the population

Patrick Aebischer, Johan Auwerx, Pénélope Andreux, Davide D'Amico

Background Urolithin A (UA) is produced by gut microflora from foods rich in ellagitannins. UA has been shown to improve mitochondrial health preclinically and in humans. Not everyone has a microbiome capable of producing UA, making supplementation with UA ...

2021

TGR5/Cathepsin E signaling regulates macrophage innate immune activation in liver ischemia and reperfusion injury

Kristina Schoonjans, Johan Auwerx, Qi Wang

The role and underlying mechanism of plasma membrane-bound G protein-coupled bile acid receptor (TGR5) in regulating macrophage innate immune activation during liver ischemia and reperfusion (IR) injury remains largely unclear. Here, we demonstrated that T ...

2021

Urolithin A improves muscle function by inducing mitophagy in muscular dystrophy

Johan Auwerx, Pénélope Andreux, Peiling Luan, Hao Li, Davide D'Amico, Pirkka-Pekka Untamo Laurila, Martin Rainer Wohlwend, Tanes Imamura de Lima

Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy, and despite advances in genetic and pharmacological disease-modifying treatments, its management remains a major challenge. Mitochondrial dysfunction contributes to DMD, yet the mecha ...

AMER ASSOC ADVANCEMENT SCIENCE2021

Acute RyR1 Ca2+ leak enhances NADH-linked mitochondrial respiratory capacity

Johan Auwerx, Umberto De Marchi, Tanes Imamura de Lima

Sustained ryanodine receptor (RyR) Ca2+ leak is associated with pathological conditions such as heart failure or skeletal muscle weakness. We report that a single session of sprint interval training (SIT), but not of moderate intensity continuous training ...

Nature Portfolio2021

GCN5 maintains muscle integrity by acetylating YY1 to promote dystrophin expression

Elena Katsyuba, Johan Auwerx, Hongbo Zhang

Protein lysine acetylation is a post-translational modification that regulates protein structure and function. It is targeted to proteins by lysine acetyltransferases (KATs) or removed by lysine deacetylases. This work identifies a role for the KAT enzyme ...

Rockefeller University Press2021

Pancreatic Sirtuin 3 Deficiency Promotes Hepatic Steatosis by Enhancing 5-Hydroxytryptamine Synthesis in Mice With Diet-Induced Obesity

Kristina Schoonjans, Johan Auwerx

Sirtuin 3 (SIRT3) is a protein deacetylase regulating beta-cell function through inhibiting oxidative stress in obese and diabetic mice, but the detailed mechanism and potential effect of beta-cell-specific SIRT3 on metabolic homeostasis, and its potential ...

AMER DIABETES ASSOC2021

Differential role of nicotinamide adenine dinucleotide deficiency in acute and chronic kidney disease

Joseph Rutkowski, Renuga Devi Rajaram, Elena Katsyuba, Johan Auwerx, Adrienne Joëlle Laurence Mottis

Background. Nicotinamide adenine dinucleotide (NAD(+)) is a ubiquitous coenzyme involved in electron transport and a cosubstrate for sirtuin function. NAD(+) deficiency has been demonstrated in the context of acute kidney injury (AKI). Methods. We studied ...

2021

TGR5 Regulates Macrophage Inflammation in Nonalcoholic Steatohepatitis by Modulating NLRP3 Inflammasome Activation

Kristina Schoonjans, Johan Auwerx

Nonalcoholic steatohepatitis (NASH) is a chronic liver disease associated with dysregulation of liver metabolism and inflammation. G-protein coupled bile acid receptor 1 (TGR5) is a cell surface receptor that is involved in multiple metabolic pathways. How ...

2021

NAD+ boosting reduces age-associated amyloidosis and restores mitochondrial homeostasis in muscle

Johan Auwerx, Hongbo Zhang, Hao Li, Vincenzo Sorrentino, Mario Romani, Changmyung Oh, Tanes Imamura de Lima

Aging is characterized by loss of proteostasis and mitochondrial homeostasis. Here, we provide bioinformatic evidence of dysregulation of mitochondrial and proteostasis pathways in muscle aging and diseases. Moreover, we show accumulation of amyloid-like d ...

2021

Nicotinamide riboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans

Johan Auwerx, Richardus Houtkooper

Background: Nicotinamide riboside (NR) is an NAD(+) precursor that boosts cellular NAD(+) concentrations. Preclinical studies have shown profound metabolic health effects after NR supplementation. ...

OXFORD UNIV PRESS2020

A conserved role of CBP/p300 in mitochondrial stress response and longevity

Johan Auwerx, Yang Li

WILEY2020

Inhibition of mitophagy drives macrophage activation and antibacterial defense during sepsis

Johan Auwerx, Antoine Jalil

Mitochondria have emerged as key actors of innate and adaptive immunity. Mitophagy has a pivotal role in cell homeostasis, but its contribution to macrophage functions and host defense remains to be delineated. Here, we showed that lipopolysaccharide (LPS) ...

AMER SOC CLINICAL INVESTIGATION INC2020

Gene replacement therapy provides benefit in an adult mouse model of Leigh syndrome

Johan Auwerx

Mutations in nuclear-encoded mitochondrial genes are responsible for a broad spectrum of disorders among which Leigh syndrome is the most common in infancy. No effective therapies are available for this severe disease mainly because of the limited capabili ...

2020

Sirt6 deletion in bone marrow-derived cells increases atherosclerosis - Central role of macrophage scavenger receptor 1

Matthias Alexander Sokrates Stein, Johan Auwerx, Julien Weber, Tasneem Arsiwala

Aims: Sirtuin 6 (Sirt6) is a NAD(+)-dependent deacetylase that plays a key role in DNA repair, inflammation and lipid regulation. Sirt6-null mice show severe metabolic defects and accelerated aging. Macrophage-foam cell formation via scavenger receptors is ...

2020

The Gene-Regulatory Footprint of Aging Highlights Conserved Central Regulators

Johan Auwerx, Richardus Houtkooper, Maroun Bou Sleiman, Xu Wang, Pooja Jha

Many genes and pathways have been linked to aging, yet our understanding of underlying molecular mechanisms is still lacking. Here, we measure changes in the transcriptome, histone modifications, and DNA methylome in three metabolic tissues of adult and ag ...

2020

TBK1 phosphorylates mutant Huntingtin and suppresses its aggregation and toxicity in Huntington's disease models

Hilal Lashuel, Anass Chiki, Johan Auwerx, Ramanath Narayana Hegde, Laurent Mouchiroud, Lara Petricca

Phosphorylation of the N‐terminal domain of the huntingtin (HTT ) protein has emerged as an important regulator of its localization, structure, aggregation, clearance and toxicity. However, validation of the effect of bona fide phosphorylation in vivo and ...

2020

Confounding factors from inducible systems for spatiotemporal gene expression regulation

Johan Auwerx, Richardus Houtkooper

Spatiotemporally regulated targeted gene manipulation is a common way to study the effect of gene variants on phenotypic traits, but the Cre/loxP and Tet-On/Tet-Off systems can affect whole-organism physiology and function due to off-target effects. We hig ...

Rockefeller University Press2020

Mouse Systems Genetics as a Prelude to Precision Medicine

Johan Auwerx, Hao Li

Mouse models have been instrumental in understanding human disease biology and proposing possible new treatments. The precise control of the environment and genetic composition of mice allows more rigorous observations, but limits the generalizability and ...

2020

Macrophage NCOR1 Deficiency Ameliorates Myocardial Infarction and Neointimal Hyperplasia in Mice

Johan Auwerx, Hongwei Zhu, Yan Liu, Yuan Liu, Shuai Shao

Background NCOR1 (nuclear receptor corepressor 1) is an essential coregulator of gene transcription. It has been shown that NCOR1 in macrophages plays important roles in metabolic regulation. However, the function of macrophage NCOR1 in response to myocard ...

2020

Asperuloside Improves Obesity and Type 2 Diabetes through Modulation of Gut Microbiota and Metabolic Signaling

Johan Auwerx, Qi Zhu

Asperuloside (ASP) is an iridoid glycoside that is extracted from Eucommia leaves. Eucommia is used in traditional Chinese medicine and has a long history of benefits on health and longevity. Here, we investigated the impact of ASP on obesity-related metab ...

2020

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