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Selective small molecule inhibitor of the Mycobacterium tuberculosis fumarate hydratase reveals an allosteric regulatory site.
Monica Kasbekar, Gerhard Fischer, Bryan T Mott, Adam Yasgar, Marko Hyvönen, Helena IM Boshoff, Chris Abell, Clifton E Barry, Craig J Thomas
Jun 30, 2016
Disruption of the TCA cycle reveals an ATF4-dependent integration of redox and amino acid metabolism.
Dylan Gerard Ryan, Ming Yang, Hiran A Prag, Giovanny Rodriguez Blanco, Efterpi Nikitopoulou, Marc Segarra-Mondejar, Christopher A Powell, Tim Young, Nils Burger, Jan Lj Miljkovic, Michal Minczuk, Michael P Murphy, Alex Von Kriegsheim, Christian Frezza
Jan 28, 2022
The Tricarboxylic Acid (TCA) Cycle is arguably the most critical metabolic cycle in physiology and exists as an essential interface coordinating cellular metabolism, bioenergetics, and redox homeostasis. Despite decades of...
Fumarate Hydratase Loss Causes Combined Respiratory Chain Defects.
Petros A Tyrakis, Marie E Yurkovich, Marco Sciacovelli, Evangelia K Papachristou, Hannah R Bridges, Edoardo Gaude, Alexander Schreiner, Clive D'Santos, Judy Hirst, Juan Hernandez-Fernaud, Roger Springett, John R Griffiths, Christian Frezza
May 22, 2018
Fumarate hydratase (FH) is an enzyme of the tricarboxylic acid (TCA) cycle mutated in hereditary and sporadic cancers. Despite recent advances in understanding its role in tumorigenesis, the effects of FH loss on mitochondrial...
Fumarate induces vesicular release of mtDNA to drive innate immunity.
Vincent Zecchini, Vincent Paupe, Irene Herranz-Montoya, Joëlle Janssen, Inge MN Wortel, Jordan L Morris, Ashley Ferguson, Suvagata Roy Chowdury, Marc Segarra-Mondejar, Ana SH Costa, Gonçalo C Pereira, Laura Tronci, Timothy Young, Efterpi Nikitopoulou, Ming Yang, Dóra Bihary, Federico Caicci, Shun Nagashima, Alyson Speed, Kalliopi Bokea, Zara Baig, Shamith Samarajiwa, Maxine Tran, Thomas Mitchell, Mark Johnson, Julien Prudent, Christian Frezza
Mar 16, 2023
Nuclear ARRB1 induces pseudohypoxia and cellular metabolism reprogramming in prostate cancer.
Vincent Zecchini, Basetti Madhu, Roslin Russell, Nelma Pértega-Gomes, Anne Warren, Edoardo Gaude, Joana Borlido, Rory Stark, Heather Ireland-Zecchini, Roheet Rao, Helen Scott, Joan Boren, Charlie Massie, Mohammad Asim, Kevin Brindle, John Griffiths, Christian Frezza, David E Neal, Ian G Mills
Nov 16, 2017
Tumour cells sustain their high proliferation rate through metabolic reprogramming, whereby cellular metabolism shifts from oxidative phosphorylation to aerobic glycolysis, even under normal oxygen levels. Hypoxia-inducible...
adaptor Hypoxia metabolism Prostate Transcription Arrestins Chromatin Immunoprecipitation Fluorescent Antibody Technique Fumarate Hydratase Gas Chromatography-Mass Spectrometry Gene Expression Profiling Humans Hypoxia-Inducible Factor 1 alpha Subunit Immunoblotting Immunohistochemistry Magnetic Resonance Spectroscopy Male Metabolic Networks and Pathways Metabolomics Models Biological Prostatic Neoplasms RNA Interference Succinate Dehydrogenase Tissue Array Analysis beta-Arrestin 1 beta-Arrestins
Fumarate metabolic signature for the detection of Reed Syndrome in humans
Ruth T Casey, Mary A McLean, Benjamin G Challis, Terri P McVeigh, Anne Y Warren, Lee Mendil, Richard Houghton, Stefano De Sanctis, Vasilis Kosmoliaptsis, Richard N Sandford, Ferdia A Gallagher, Eamonn R Maher
Oct 23, 2019
mTORC1 Upregulation Leads to Accumulation of the Oncometabolite Fumarate in a Mouse Model of Renal Cell Carcinoma.
Luca Drusian, Elisa Agnese Nigro, Valeria Mannella, Roberto Pagliarini, Monika Pema, Ana SH Costa, Fabio Benigni, Alessandro Larcher, Marco Chiaravalli, Edoardo Gaude, Francesco Montorsi, Umberto Capitanio, Giovanna Musco, Christian Frezza, Alessandra Boletta
Nov 01, 2018
Renal cell carcinomas (RCCs) are common cancers diagnosed in more than 350,000 people each year worldwide. Several pathways are de-regulated in RCCs, including mTORC1. However, how mTOR drives tumorigenesis in this context is...
TCA cycle cancer metabolism cancer signaling epithelial transformation Fumarate Hydratase Metabolic reprogramming papillary carcinoma rapamycin renal cancer renal cysts Animals Carcinoma Renal Cell Cells Cultured Female Fumarate Hydratase Fumarates Humans Kidney Neoplasms Male Mechanistic Target of Rapamycin Complex 1 Mice Mice Inbred C57BL Tuberous Sclerosis Complex 1 Protein Up-Regulation
Fumarate is an epigenetic modifier that elicits epithelial-to-mesenchymal transition.
Marco Sciacovelli, Emanuel Gonçalves, Timothy Isaac Johnson, Vincent Roberto Zecchini, Ana Sofia Henriques da Costa, Edoardo Gaude, Alizee Vercauteren Drubbel, Sebastian Julian Theobald, Sandra Riekje Abbo, Maxine Gia Binh Tran, Vinothini Rajeeve, Simone Cardaci, Sarah Foster, Haiyang Yun, Pedro Cutillas, Anne Warren, Vincent Gnanapragasam, Eyal Gottlieb, Kristian Franze, Brian Huntly, Eamonn Richard Maher, Patrick Henry Maxwell, Julio Saez-Rodriguez, Christian Frezza
Sep 30, 2016
Fumarate induces vesicular release of mtDNA to drive innate immunity.
Vincent Zecchini, Vincent Paupe, Irene Herranz-Montoya, Joëlle Janssen, Inge MN Wortel, Jordan L Morris, Ashley Ferguson, Suvagata Roy Chowdury, Marc Segarra-Mondejar, Ana SH Costa, Gonçalo C Pereira, Laura Tronci, Timothy Young, Efterpi Nikitopoulou, Ming Yang, Dóra Bihary, Federico Caicci, Shun Nagashima, Alyson Speed, Kalliopi Bokea, Zara Baig, Shamith Samarajiwa, Maxine Tran, Thomas Mitchell, Mark Johnson, Julien Prudent, Christian Frezza
Apr 08, 2023
Mutations in fumarate hydratase (FH) cause hereditary leiomyomatosis and renal cell carcinoma1. Loss of FH in the kidney elicits several oncogenic signalling cascades through the accumulation of the oncometabolite fumarate2....
Post-translational regulation of metabolism in fumarate hydratase deficient cancer cells.
Emanuel Gonçalves, Marco Sciacovelli, Ana SH Costa, Maxine Gia Binh Tran, Timothy Isaac Johnson, Daniel Machado, Christian Frezza, Julio Saez-Rodriguez
Feb 13, 2018
Deregulated signal transduction and energy metabolism are hallmarks of cancer and both play a fundamental role in tumorigenesis. While it is increasingly recognised that signalling and metabolism are highly interconnected, the...
Hereditary renal cell carcinoma syndromes
Eamonn R Maher
Jul 10, 2018
PURPOSE: Genetic factors have been implicated in the pathogenesis of renal cell carcinoma (RCC), with around 3% of cases having a family history. A greater knowledge of the genetics of inherited RCC has the potential to...
Familial syndromic renal cancer Genetics von Hippel–Lindau review Age of Onset Birt-Hogg-Dube Syndrome Carcinoma Renal Cell Disease Management Early Detection of Cancer Fumarate Hydratase Humans Kidney Neoplasms Leiomyomatosis Neoplasms Multiple Primary Neoplastic Syndromes Hereditary Proto-Oncogene Proteins Proto-Oncogene Proteins c-met Skin Neoplasms Succinate Dehydrogenase Tumor Suppressor Proteins Ubiquitin Thiolesterase Uterine Neoplasms Von Hippel-Lindau Tumor Suppressor Protein von Hippel-Lindau Disease
Targeting of Fumarate Hydratase from Mycobacterium tuberculosis Using Allosteric Inhibitors with a Dimeric-Binding Mode.
Andrew J Whitehouse, M Daben J Libardo, Monica Kasbekar, Paul D Brear, Gerhard Fischer, Craig J Thomas, Clifton E Barry, Helena IM Boshoff, Anthony G Coyne, Chris Abell
Sep 16, 2019
With the growing worldwide prevalence of antibiotic-resistant strains of tuberculosis (TB), new targets are urgently required for the development of treatments with novel modes of action. Fumarate hydratase (fumarase), a...
Fumarate hydratase loss promotes mitotic entry in the presence of DNA damage after ionising radiation.
An altered response to DNA damage is commonly associated with genomic instability, a hallmark of cancer. Fumarate hydratase (FH) was recently characterised as a DNA repair factor required in non-homologous end-joining (NHEJ)...