Publications by Xu Wang | EPFL Graph Search

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

MicroRNA-204-5p modulates mitochondrial biogenesis in C2C12 myotubes and associates with oxidative capacity in humans

Xu Wang

Using an unbiased high-throughput microRNA (miRNA)-silencing screen combined with functional readouts for mitochondrial oxidative capacity in C2C12 myocytes, we previously identified 19 miRNAs as putative regulators of skeletal muscle mitochondrial metabol ...

2020

MicroRNA-382 silencing induces a mitonuclear protein imbalance and activates the mitochondrial unfolded protein response in muscle cells

Johan Auwerx, Norman Lionel Moullan, Pénélope Andreux, Xu Wang

Proper mitochondrial function plays a central role in cellular metabolism. Various diseases as well as aging are associated with diminished mitochondrial function. Previously, we identified 19 miRNAs putatively involved in the regulation of mitochondrial m ...

2019

An Integrated Systems Genetics and Omics Toolkit to Probe Gene Function

Stephan Morgenthaler, Kristina Schoonjans, Johan Auwerx, Maroun Bou Sleiman, Hongbo Zhang, Daria Rukina, Karim Laurent Gariani, Xu Wang, Tao Lin, Peiling Luan, Hao Li, Vincenzo Sorrentino, Qingyao Huang, Naveed Ziari

2018

Plasma Membrane-bound G Protein-coupled Bile Acid Receptor Attenuates Liver Ischemia/Reperfusion Injury Via the Inhibition of Toll-like Receptor 4 Signaling in Mice

Kristina Schoonjans, Johan Auwerx, Xu Wang

The plasma membrane-bound G protein-coupled bile acid receptor (TGR5) displays varied levels of expression in different tissues. TGR5-induced liver protection has been demonstrated during several liver diseases, except during ischemia/reperfusion injury (I ...

Wiley2017

Impaired SUMOylation of nuclear receptor LRH-1 promotes nonalcoholic fatty liver disease

Matthias Alexander Sokrates Stein, Kristina Schoonjans, Dongryeol Ryu, Maaike Hélène Oosterveer, Pan Xu, Xu Wang, Vera Monica Lemos Da Silva, Hadrien Charles Edouard Demagny

Hepatic steatosis is caused by metabolic imbalances that could be explained in part by an increase in de novo lipogenesis that results from increased sterol element binding protein 1 (SREBP-1) activity. The nuclear receptor liver receptor homolog 1 (LRH-1) ...

Amer Soc Clinical Investigation Inc2017

An unbiased silencing screen in muscle cells identifies miR-320a, miR-150, miR-196b, and miR-34c as regulators of skeletal muscle mitochondria! metabolism

Johan Auwerx, Pénélope Andreux, Xu Wang

Objective: Strategies improving skeletal muscle mitochondrial capacity are commonly paralleled by improvements in (metabolic) health. We and others previously identified microRNAs regulating mitochondrial oxidative capacity, but data in skeletal muscle are ...

Elsevier Science Bv2017

Systems Phytohormone Responses to Mitochondrial Proteotoxic Stress

Johan Auwerx, Xu Wang

Mitochondrial function is controlled by two separate genomes. This feature makes mitochondria prone to proteotoxic stress when a stoichiometric imbalance occurs in the protein complexes that perform oxidative phosphorylation, which consist of both nucleara ...

Cell Press2017

Enhanced Respiratory Chain Supercomplex Formation in Response to Exercise in Human Skeletal Muscle

Chiara Greggio, Johan Auwerx, Carlos Canto Alvarez, Xu Wang, Pooja Jha

Mitochondrial dysfunction is a hallmark of multiple metabolic complications. Physical activity is known to increase mitochondrial content in skeletal muscle, counteracting age-related decline in muscle function and protecting against metabolic and cardiova ...

Cell Press2017

LRH-1-dependent programming of mitochondrial glutamine processing drives liver cancer

Arnaud Comment, Matthias Alexander Sokrates Stein, Kristina Schoonjans, Johan Auwerx, Norman Lionel Moullan, Dongryeol Ryu, Maaike Hélène Oosterveer, Emine Can, Pan Xu, Xu Wang, Hadrien Charles Edouard Demagny

Various tumors develop addiction to glutamine to support uncontrolled cell proliferation. Here we identify the nuclear receptor liver receptor homolog 1 (LRH-1) as a key regulator in the process of hepatic tumorigenesis through the coordination of a noncan ...

Cold Spring Harbor Laboratory2016

NAD(+) repletion improves muscle function in muscular dystrophy and counters global PARylation

Johan Auwerx, Carlos Canto Alvarez, Dongryeol Ryu, Laurent Mouchiroud, Hongbo Zhang, Keir Joe Menzies, Karim Laurent Gariani, Xu Wang, Vincenzo Sorrentino

Neuromuscular diseases are often caused by inherited mutations that lead to progressive skeletal muscle weakness and degeneration. In diverse populations of normal healthy mice, we observed correlations between the abundance of mRNA transcripts related to ...

Amer Assoc Advancement Science2016

NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice

Matthias Lütolf, Ruedi Aebersold, Kristina Schoonjans, Johan Auwerx, Dongryeol Ryu, Hongbo Zhang, Keir Joe Menzies, Karim Laurent Gariani, Xu Wang, Peiling Luan, Davide D'Amico

Adult stem cells (SCs) are essential for tissue maintenance and regeneration yet are susceptible to senescence during aging. We demonstrate the importance of the amount of the oxidized form of cellular nicotinamide adenine dinucleotide (NAD(+)) and its imp ...

American Association for the Advancement of Science2016

Submarine fresh groundwater discharge into Laizhou Bay comparable to the Yellow River flux

David Andrew Barry, Xu Wang, Xin Luo

Near- and off-shore fresh groundwater resources become increasingly important with the social and economic development in coastal areas. Although large scale (hundreds of km) submarine groundwater discharge (SGD) to the ocean has been shown to be of the sa ...

Nature Publishing Group2015

Phosphorylation of the nuclear receptor co-repressor 1 by protein kinase B (PKB/Akt) switches its co-repressor targets in the liver

Kristina Schoonjans, Johan Auwerx, Dongryeol Ryu, Adriano Maida, Xu Wang

The nuclear receptor corepressor 1 (NCoR1) is a transcriptional co-regulator that has wide-ranging effects on gene expression patterns. In the liver, NCoR1 represses lipid synthesis in the fasting state, whereas it inhibits the activation of PPARα upon fee ...

Wiley-Blackwell2015

Tetracyclines Disturb Mitochondrial Function across Eukaryotic Models: A Call for Caution in Biomedical Research

Michael Vincent Frochaux, Bart Deplancke, Johan Auwerx, Richardus Houtkooper, Norman Lionel Moullan, Evan Graehl Williams, Dongryeol Ryu, Adrienne Joëlle Laurence Mottis, Laurent Mouchiroud, Virginija Jovaisaite, Xu Wang

In recent years, tetracyclines, such as doxycycline, have become broadly used to control gene expression by virtue of the Tet-on/Tet-off systems. However, the wide range of direct effects of tetracycline use has not been fully appreciated. We show here tha ...

Elsevier2015

SUMOylation-Dependent LRH-1/PROX1 Interaction Promotes Atherosclerosis by Decreasing Hepatic Reverse Cholesterol Transport

Matthias Alexander Sokrates Stein, Kristina Schoonjans, Chikage Mataki, Dongryeol Ryu, Maaike Hélène Oosterveer, Pan Xu, Keir Joe Menzies, Alessia Perino, Xu Wang, Vera Monica Lemos Da Silva

Reverse cholesterol transport (RCT) is an antiatherogenic process in which excessive cholesterol from peripheral tissues is transported to the liver and finally excreted from the body via the bile. The nuclear receptor liver receptor homolog 1 (LRH-1) driv ...

Cell Press2014

A method to identify and validate mitochondrial modulators using mammalian cells and the worm C-elegans

Sabrina Bichet, Johan Auwerx, Richardus Houtkooper, Norman Lionel Moullan, Pénélope Andreux, Adrienne Joëlle Laurence Mottis, Laurent Mouchiroud, Virginija Jovaisaite, Xu Wang

Mitochondria are semi-autonomous organelles regulated by a complex network of proteins that are vital for many cellular functions. Because mitochondrial modulators can impact many aspects of cellular homeostasis, their identification and validation has pro ...

Nature Publishing Group2014