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[] Metabolic Alterations in Fumarate Hydratase Deficient Cells

University of Cambridge
20 November 2017
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Mutations of the tricarboxylic acid cycle (TCA cycle) enzyme fumarate hydratase (FH) cause the hereditary cancer syndrome Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC). FH-deficient renal cancers are highly aggressive and metastasise even when small, leading to an abysmal clinical outcome. How these cells survive without FH and how they become transformed is still under investigation. Today, I will show our data on the metabolic reprogramming triggered by the loss of FH, which induces, amongst various changes, the fumarate-mediated succination of the iron-sulfur-cluster proteins ISCU1, NFU1, and Bola1/3. Of note, this post translational modification leads to defects in iron-sulfur cluster biogenesis and complex I deficiency. These results could help to explain the profound alteration of mitochondrial metabolism in cells that lack FH.


cancer metabolism, fumarate hydratase, mitochondria

Cite this article as

Frezza, C. Metabolic Alterations in Fumarate Hydratase Deficient Cells. In Proceedings of the The 2nd International Electronic Conference on Metabolomics, 20–27 November 2017; Sciforum Electronic Conference Series, Vol. 2, 2017 ; doi:10.3390/iecm-2-04986


Author biographies

Christian Frezza
Christian Frezza is an MRC Programme Leader at the MRC Cancer Unit, University of Cambridge. He studied Medicinal Chemistry at the University of Padova, Italy, and gained his MSc in 2002, after a period of research on mitochondrial toxicity induced by photoactivable anticancer drugs. Christian then joined the laboratory of Luca Scorrano in Padova to start a PhD on mitochondrial dynamics and apoptosis. In 2008, he moved to the Beatson Institute of Cancer Research in Glasgow as recipient of an EMBO Long Term Fellowship, where he investigated the role of mitochondrial defects in tumorigenesis. He moved to the MRC Cancer Unit in 2012, to take up his current position. Christian’s research is focussed on understanding the role of altered metabolism in cancer, particularly investigating how small molecule metabolites affect the process of tumorigenesis. The major goal of his team is to exploit this knowledge to pioneer novel tools for cancer diagnosis and therapy.

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