Dysregulation of hypoxia pathways in fumarate hydratase-deficient cells is independent of defective mitochondrial metabolism.

Journal article

Mutations in the gene encoding the Krebs cycle enzyme fumarate hydratase (FH) predispose to hereditary leiomyomatosis and renal cell cancer in affected individuals. FH-associated neoplasia is characterized by defective mitochondrial function and by upregulation of transcriptional pathways mediated by hypoxia-inducible factor (HIF), although whether and by what means these processes are linked has been disputed. We analysed the HIF pathway in Fh1-/- mouse embryonic fibroblasts (MEFs), in FH-de...

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Authors: O'Flaherty, L; Adam, J; Heather, L; Zhdanov, A; Chung, Y

• Publication status: Published
• Journal: Human molecular genetics
• Volume: 19
• Issue: 19
• Pages: 3844-3851
• Publication date: 2010-10-01
• DOI: 10.1093/hmg/ddq305
• EISSN: 1460-2083
• ISSN: 0964-6906
• Language: English
• Keywords: Models, Biological; Protein Processing, Post-Translational; Signal Transduction; Humans; Fumarate Hydratase; Oxygen Consumption; Mice; Fibroblasts; Mitochondria; Hydroxylation; Animals; Proline; Cell Hypoxia; Embryo, Mammalian; Genetic Complementation Test; Hypoxia-Inducible Factor 1, alpha Subunit