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

300 shared publications

Heidelberg University

Gyorgy Szabadkai

17 shared publications

University College London

Thomas S Blacker

10 shared publications

University College London

Margaret Ashcroft

4 shared publications

University of Cambridge

Christian Frezza

3 shared publications

University of Cambridge

3
Publications
3
Reads
0
Downloads
8
Citations
Publication Record
Distribution of Articles published per year 
(2017 - 2019)
Total number of journals
published in
 
3
 
Publications
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
Article 3 Reads 2 Citations Post-translational regulation of metabolism in fumarate hydratase deficient cancer cells Emanuel Gonçalves, Marco Sciacovelli, Ana S.H. Costa, Maxine... Published: 01 January 2018
Metabolic Engineering, doi: 10.1016/j.ymben.2017.11.011
DOI See at publisher website PubMed View at PubMed ABS Show/hide abstract
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 underpinning mechanisms of their co-regulation are still largely unknown. Here we designed and acquired proteomics, phosphoproteomics, and metabolomics experiments in fumarate hydratase (FH) deficient cells and developed a computational modelling approach to identify putative regulatory phosphorylation-sites of metabolic enzymes. We identified previously reported functionally relevant phosphosites and potentially novel regulatory residues in enzymes of the central carbon metabolism. In particular, we showed that pyruvate dehydrogenase (PDHA1) enzymatic activity is inhibited by increased phosphorylation in FH-deficient cells, restricting carbon entry from glucose to the tricarboxylic acid cycle. Moreover, we confirmed PDHA1 phosphorylation in human FH-deficient tumours. Our work provides a novel approach to investigate how post-translational modifications of enzymes regulate metabolism and could have important implications for understanding the metabolic transformation of FH-deficient cancers with potential clinical applications.
Article 0 Reads 5 Citations Fumarate Hydratase Loss Causes Combined Respiratory Chain Defects Petros A. Tyrakis, Marie E. Yurkovich, Marco Sciacovelli, Ev... Published: 01 October 2017
Cell Reports, doi: 10.1016/j.celrep.2017.09.092
DOI See at publisher website PubMed View at PubMed ABS Show/hide abstract
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 metabolism are still unclear. Here, we used mouse and human cell lines to assess mitochondrial function of FH-deficient cells. We found that human and mouse FH-deficient cells exhibit decreased respiration, accompanied by a varying degree of dysfunction of respiratory chain (RC) complex I and II. Moreover, we show that fumarate induces succination of key components of the iron-sulfur cluster biogenesis family of proteins, leading to defects in the biogenesis of iron-sulfur clusters that affect complex I function. We also demonstrate that suppression of complex II activity is caused by product inhibition due to fumarate accumulation. Overall, our work provides evidence that the loss of a single TCA cycle enzyme is sufficient to cause combined RC activity dysfunction.
Top