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Christian Frezza   Dr.  Other 
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Christian Frezza published an article in January 2019.
Top co-authors See all
Julio R. Banga

389 shared publications

Bioprocess Engineering Group, IIM-CSIC, Vigo 36208, Spain

Jörg D. Hoheisel

163 shared publications

Functional Genome Analysis, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany

Christian Frezza

125 shared publications

University of Cambridge

Gyorgy Szabadkai

76 shared publications

University College London

Tomer Shlomi

44 shared publications

Department of Computer Science Technion Haifa Israel

96
Publications
26
Reads
2
Downloads
1966
Citations
Publication Record
Distribution of Articles published per year 
(2005 - 2019)
Total number of journals
published in
 
39
 
Publications See all
PREPRINT-CONTENT 0 Reads 0 Citations CHCHD4 regulates a proliferation-EMT switch in tumour cells, through respiratory complex I mediated metabolism. Luke W Thomas, Cinzia Esposito, Jenna M Stephen, Ana Sh Cost... Published: 07 January 2019
bioRxiv, doi: 10.1101/513531
DOI See at publisher website ABS Show/hide abstract
BACKGROUND: Mitochondrial metabolism involves oxidative phosphorylation (OXPHOS) via the respiratory chain and is required for the maintenance of tumour cell proliferation and regulation of epithelial/mesenchymal transition (EMT) related phenotypes through mechanisms that are not fully understood. The essential mitochondrial import protein coiled-coil helix coiled-coil helix domain-containing protein 4 (CHCHD4) controls respiratory chain complex activity and oxygen consumption, and regulates the growth of tumours in vivo. In this study we interrogate the role of CHCHD4 regulated respiratory chain activity and metabolism in tumour cell proliferation and EMT-related phenotypes. RESULTS: We show that CHCHD4 is essential for the proliferation of tumour cells irrespective of their aetiology. In human tumours, elevated CHCHD4 expression is correlated with a mitochondrial OXPHOS gene signature and with a proliferative gene signature associated with the mTORC1 signalling pathway. Elevated CHCHD4 increases tumour cell proliferation, in a manner that is dependent on complex I (CI) activity, glutamine consumption and mTORC1 activation. CHCHD4 expression is inversely correlated with EMT gene expression both in vitro and in vivo. Finally, we show CHCHD4 regulates the intracellular distribution of the EMT marker vimentin, in a CI mediated manner. CONCLUSIONS: CHCHD4 regulates tumour cell proliferation and metastatic (EMT related) phenotypes through its control of CI-mediated mitochondrial metabolism.
Article 0 Reads 0 Citations Coupling Krebs cycle metabolites to signalling in immunity and cancer Dylan G. Ryan, Michael P. Murphy, Christian Frezza, Hiran A.... Published: 30 December 2018
Nature Metabolism, doi: 10.1038/s42255-018-0014-7
DOI See at publisher website
Article 0 Reads 0 Citations Deletion of myeloid IRS2 enhances adipose tissue sympathetic nerve function and limits obesity Marie-Therese Rached, Steven J. Millership, Silvia M.A. Pedr... Published: 28 November 2018
Molecular Metabolism, doi: 10.1016/j.molmet.2018.11.010
DOI See at publisher website PubMed View at PubMed ABS Show/hide abstract
Sympathetic nervous system and immune cell interactions play key roles in the regulation of metabolism. For example, recent convergent studies have shown that macrophages regulate obesity through brown adipose tissue (BAT) activation and beiging of white adipose tissue (WAT) via effects upon local catecholamine availability. However, these studies have raised issues about the underlying mechanisms involved including questions regarding the production of catecholamines by macrophages, the role of macrophage polarization state and the underlying intracellular signaling pathways in macrophages that might mediate these effects. To address such issues we generated mice lacking Irs2, which mediates the effects of insulin and interleukin 4, specifically in LyzM expressing cells (Irs2LyzM−/− mice). These animals displayed obesity resistance and preservation of glucose homeostasis on high fat diet feeding due to increased energy expenditure via enhanced BAT activity and WAT beiging. Macrophages per se did not produce catecholamines but Irs2LyzM−/− mice displayed increased sympathetic nerve density and catecholamine availability in adipose tissue. Irs2-deficient macrophages displayed an anti-inflammatory transcriptional profile and alterations in genes involved in scavenging catecholamines and supporting increased sympathetic innervation. Our studies identify a critical macrophage signaling pathway involved in the regulation of adipose tissue sympathetic nerve function that, in turn, mediates key neuroimmune effects upon systemic metabolism. The insights gained may open therapeutic opportunities for the treatment of obesity.
Article 0 Reads 0 Citations Dissection of metabolic reprogramming in polycystic kidney disease reveals coordinated rewiring of bioenergetic pathways Christine Podrini, Isaline Rowe, Roberto Pagliarini, Ana S. ... Published: 16 November 2018
Communications Biology, doi: 10.1038/s42003-018-0200-x
DOI See at publisher website PubMed View at PubMed ABS Show/hide abstract
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disorder caused by loss-of-function mutations in PKD1 or PKD2. Increased glycolysis is a prominent feature of the disease, but how it impacts on other metabolic pathways is unknown. Here, we present an analysis of mouse Pkd1 mutant cells and kidneys to investigate the metabolic reprogramming of this pathology. We show that loss of Pkd1 leads to profound metabolic changes that affect glycolysis, mitochondrial metabolism, and fatty acid synthesis (FAS). We find that Pkd1-mutant cells preferentially use glutamine to fuel the TCA cycle and to sustain FAS. Interfering with either glutamine uptake or FAS retards cell growth and survival. We also find that glutamine is diverted to asparagine via asparagine synthetase (ASNS). Transcriptional profiling of PKD1-mutant human kidneys confirmed these alterations. We find that silencing of Asns is lethal in Pkd1-mutant cells when combined with glucose deprivation, suggesting therapeutic approaches for ADPKD.
PREPRINT-CONTENT 0 Reads 0 Citations Tumor pre-conditioning of draining lymph node stroma by lactic acid Angela Riedel, Jonathan Swietlik, David Shorthouse, Lisa Haa... Published: 12 October 2018
bioRxiv, doi: 10.1101/442137
DOI See at publisher website
Article 0 Reads 4 Citations Genome editing in mitochondria corrects a pathogenic mtDNA mutation in vivo Payam A. Gammage, Carlo Viscomi, Marie-Lune Simard, Ana S. H... Published: 24 September 2018
Nature Medicine, doi: 10.1038/s41591-018-0165-9
DOI See at publisher website
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