Loss of succinate dehydrogenase activity results in dependency on pyruvate carboxylation for cellular anabolism

Nature Communications

Volumn 6, Issue , 2015, Pages

  Lussey Lepoutre, Charlotte ^a,b,c   Hollinshead, Kate E R ^d   Ludwig, Christian ^d   Menara, Mélanie ^a,b   Morin, Aurélie ^a,b   Castro Vega, Luis Jaime ^a,b   Parker, Seth J ^e   Janin, Maxime ^b,f,g   Martinelli, Cosimo ^a,b   Ottolenghi, Chris ^b,f,g   Metallo, Christian ^e   Gimenez Roqueplo, Anne Paule ^a,b,c   Favier, Judith ^a,b   Tennant, Daniel A ^d  

^a PARIS CARDIOVASCULAR RESEARCH CENTER   (France)

^b UNIVERSITÉ PARIS DESCARTES   (France)

^c HÔPITAL EUROPÉEN GEORGES POMPIDOU   (France)

^d UNIVERSITY OF BIRMINGHAM   (United Kingdom)

^e UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^f HÔPITAL NECKER ENFANTS MALADES   (France)

^g INSERM   (France)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; CELLS AND CELL COMPONENTS; ENZYME ACTIVITY; HOMEOSTASIS; METABOLISM; PHENOTYPE; PHENOTYPIC PLASTICITY; VULNERABILITY;

ASPARTIC ACID; MEMBRANE PROTEIN; PYRUVIC ACID; SDHD PROTEIN, HUMAN; SDHD PROTEIN, MOUSE; SUCCINATE DEHYDROGENASE; SUCCINATE DEHYDROGENASE (UBIQUINONE);

ANIMAL; ENZYMOLOGY; GENETICS; HUMAN; KNOCKOUT MOUSE; METABOLISM; MOUSE; NEUROENDOCRINE TUMOR; OXIDATIVE PHOSPHORYLATION; PARAGANGLIOMA;

ANIMALS; ASPARTIC ACID; ELECTRON TRANSPORT COMPLEX II; HUMANS; MEMBRANE PROTEINS; MICE; MICE, KNOCKOUT; NEUROENDOCRINE TUMORS; OXIDATIVE PHOSPHORYLATION; PARAGANGLIOMA; PYRUVIC ACID; SUCCINATE DEHYDROGENASE;

EID: 84946210278     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms9784     Document Type: Article

References (40)

1. Astuti, D., et al. Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma. Am. J. Hum. Genet. 69, 49-54 (2001).
2. Baysal, B. E., et al. Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science 287, 848-851 (2000).
3. Burnichon, N., et al. SDHA is a tumor suppressor gene causing paraganglioma. Hum. Mol. Genet. 19, 3011-3020 (2010).
4. Hao, H. X., et al. SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma. Science 325, 1139-1142 (2009).
5. Niemann, S. & Muller, U. Mutations in SDHC cause autosomal dominant paraganglioma, type 3. Nat. Genet. 26, 268-270 (2000).
6. Gimenez-Roqueplo, A. P., et al. Mutations in the SDHB gene are associated with extra-adrenal and/or malignant phaeochromocytomas. Cancer Res. 63, 5615-5621 (2003).
7. Amar, L., et al. Succinate dehydrogenase B gene mutations predict survival in patients with malignant pheochromocytomas or paragangliomas. J. Clin. Endocrinol. Metab. 92, 3822-3828 (2007).
8. Gimenez-Roqueplo, A. P., et al. The R22X mutation of the SDHD gene in hereditary paraganglioma abolishes the enzymatic activity of complex II in the mitochondrial respiratory chain and activates the hypoxia pathway. Am. J. Hum. Genet. 69, 1186-1197 (2001).
9. Gimenez-Roqueplo, A. P., et al. Functional consequences of a SDHB gene mutation in an apparently sporadic pheochromocytoma. J. Clin. Endocrinol. Metab. 87, 4771-4774 (2002).
10. Douwes Dekker, P. B., et al. SDHD mutations in head and neck paragangliomas result in destabilization of complex II in the mitochondrial respiratory chain with loss of enzymatic activity and abnormal mitochondrial morphology. J. Pathol. 201, 480-486 (2003).
11. Selak, M. A., et al. Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase. Cancer cell 7, 77-85 (2005).
12. Letouze, E., et al. SDH mutations establish a hypermethylator phenotype in paraganglioma. Cancer cell 23, 739-752 (2013).
13. Yang, M., Soga, T. & Pollard, P. J. Oncometabolites: linking altered metabolism with cancer. J. Clin. Invest. 123, 3652-3658 (2013).
14. Baysal, B. E. On the association of succinate dehydrogenase mutations with hereditary paraganglioma. Trends Endocrinol. Metab. 14, 453-459 (2003).
15. Pollard, P. J., Wortham, N. C. & Tomlinson, I. P. The TCA cycle and tumorigenesis: the examples of fumarate hydratase and succinate dehydrogenase. Ann. Med. 35, 632-639 (2003).
16. Pollard, P. J., et al. Accumulation of Krebs cycle intermediates and overexpression of HIF1alpha in tumours which result from germline FH and SDH mutations. Hum. Mol. Genet. 14, 2231-2239 (2005).
17. Favier, J., et al. The Warburg effect is genetically determined in inherited pheochromocytomas. PloS ONE 4, e7094 (2009).
18. Frezza, C., et al. Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase. Nature 477, 225-228 (2011).
19. Zheng, L., et al. Reversed argininosuccinate lyase activity in fumarate hydratasedeficient cancer cells. Cancer Metab. 1, 12 (2013).
20. Metallo, C. M., et al. Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature 481, 380-384 (2012).
21. Wise, D. R., et al. Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of alpha-ketoglutarate to citrate to support cell growth and viability. Proc. Natl Acad. Sci. USA 108, 19611-19616 (2011).
22. Mullen, A. R., et al. Reductive carboxylation supports growth in tumour cells with defective mitochondria. Nature 481, 385-388 (2012).
23. Possemato, R., et al. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature 476, 346-350 (2011).
24. Leithner, K., et al. PCK2 activation mediates an adaptive response to glucose depletion in lung cancer. Oncogene 34, 1044-1050 (2015).
25. Li, Y., et al. Upregulation of cytosolic phosphoenolpyruvate carboxykinase is a critical metabolic event in melanoma cells that repopulate tumors. Cancer Res. 75, 1191-1196 (2015).
26. Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144, 646-674 (2011).
27. Gaude, E. & Frezza, C. Defects in mitochondrial metabolism and cancer. Cancer Metab. 2, 10 (2014).
28. Plouin, P. F., Gimenez-Roqueplo, A. P. & Bertagna, X. [COMETE, a network for the study and management of hypersecreting adrenal tumors]. Bull. Acad. Natl Med. 192, 73-82 ; discussion 83-75 (2008).
29. Lenders, J. W., et al. Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 99, 1915-1942 (2014).
30. Burnichon, N., et al. Integrative genomic analysis reveals somatic mutations in pheochromocytoma and paraganglioma. Hum. Mol. Genet. 20, 3974-3985 (2011).
31. Castro-Vega, L. J., et al. Multi-omics analysis defines core genomic alterations in pheochromocytomas and paragangliomas. Nat. Commun. 6, 6044 (2015).
32. Ludwig, C. & Gunther, U. L. MetaboLab -advanced NMR data processing and analysis for metabolomics. BMC Bioinformatics 12, 366 (2011).
33. Delaglio, F., et al. Nmrpipe -a multidimensional spectral processing system based on unix pipes. J. Biomol. NMR 6, 277-293 (1995).
34. Kazimierczuk, K. & Orekhov, V. Y. Accelerated NMR Spectroscopy by Using Compressed Sensing. Angew. Chem. Int. Edit. 50, 5556-5559 (2011).
35. Orekhov, V. Y. & Jaravine, V. A. Analysis of non-uniformly sampled spectra with multi-dimensional decomposition. Prog. Nucl. Mag. Res. Sp. 59, 271-292 (2011).
36. Smith, S. A., Levante, T. O., Meier, B. H. & Ernst, R. R. Computer-simulations in magnetic-resonance -an object-oriented programming approach. J. Magn. Reson. Ser. A 106, 75-105 (1994).
37. Wishart, D. S., et al. HMDB: the human metabolome database. Nucleic Acids Res. 35, D521-D526 (2007).
38. Lewis, C. A., et al. Tracing compartmentalized NADPH metabolism in the cytosol and mitochondria of mammalian cells. Mol. Cell 55, 253-263 (2014).
39. Fernandez, C. A., Des Rosiers, C., Previs, S. F., David, F. & Brunengraber, H. Correction of 13C mass isotopomer distributions for natural stable isotope abundance. J. Mass Spectrom. 31, 255-262 (1996).
40. Favier, J., Kempf, H., Corvol, P. & Gasc, J. Cloning and expression pattern of EPAS1 in the chicken embryo. Colocalization with tyrosine hydroxylase. FEBS Lett. 462, 19-24 (1999).