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

Research output: Contribution to journalArticlepeer-review

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Loss of succinate dehydrogenase activity results in dependency on pyruvate carboxylation for cellular anabolism. / Lussey-Lepoutre, Charlotte; Hollinshead, Kate; Ludwig, Christian; Menara, Melanie ; Morin, Aurelie; Castro-Vega, Luis-Jaime; Parker, Seth J.; Janin, Maxime; Martinelli, Cosimo; Ottolenghi, Chris; Metallo, Christian; Gimenez-Roqueplo, Anne-Paule ; Favier, Judith; Tennant, Daniel.

In: Nature Communications, Vol. 6, 8784, 02.11.2015.

Research output: Contribution to journalArticlepeer-review

Harvard

Lussey-Lepoutre, C, Hollinshead, K, Ludwig, C, Menara, M, Morin, A, Castro-Vega, L-J, Parker, SJ, Janin, M, Martinelli, C, Ottolenghi, C, Metallo, C, Gimenez-Roqueplo, A-P, Favier, J & Tennant, D 2015, 'Loss of succinate dehydrogenase activity results in dependency on pyruvate carboxylation for cellular anabolism', Nature Communications, vol. 6, 8784. https://doi.org/10.1038/ncomms9784

APA

Lussey-Lepoutre, C., Hollinshead, K., Ludwig, C., Menara, M., Morin, A., Castro-Vega, L-J., Parker, S. J., Janin, M., Martinelli, C., Ottolenghi, C., Metallo, C., Gimenez-Roqueplo, A-P., Favier, J., & Tennant, D. (2015). Loss of succinate dehydrogenase activity results in dependency on pyruvate carboxylation for cellular anabolism. Nature Communications, 6, [8784]. https://doi.org/10.1038/ncomms9784

Vancouver

Author

Lussey-Lepoutre, Charlotte ; Hollinshead, Kate ; Ludwig, Christian ; Menara, Melanie ; Morin, Aurelie ; Castro-Vega, Luis-Jaime ; Parker, Seth J. ; Janin, Maxime ; Martinelli, Cosimo ; Ottolenghi, Chris ; Metallo, Christian ; Gimenez-Roqueplo, Anne-Paule ; Favier, Judith ; Tennant, Daniel. / Loss of succinate dehydrogenase activity results in dependency on pyruvate carboxylation for cellular anabolism. In: Nature Communications. 2015 ; Vol. 6.

Bibtex

@article{e17b099ee34745d9bdf9d281287932d7,
title = "Loss of succinate dehydrogenase activity results in dependency on pyruvate carboxylation for cellular anabolism",
abstract = "The tricarboxylic acid (TCA) cycle is a central metabolic pathway responsible for supplying reducing potential for oxidative phosphorylation and anabolic substrates for cell growth, repair and proliferation. As such, it might be considered as essential for the ongoing viability and proliferation of a cell or tissue. However, since the first report in 2000 of an inactivating mutation in the TCA cycle enzyme complex, succinate dehydrogenase (SDH) in paraganglioma (PGL), it has become clear that some cells and tissues are not only able to survive with a truncated TCA cycle, but they are also able to support the cell growth and proliferative phenotype observed in tumours. Here, we show that loss of SDH activity leads to changes in the metabolism of non-essential amino acids: in particular, we demonstrate that pyruvate carboxylase is essential to re-fill the depleted pool of aspartate in SDH-deficient cells. Our work demonstrates that the loss of SDH reduces the metabolic plasticity of cells, indicating vulnerabilities that can be targeted therapeutically.",
author = "Charlotte Lussey-Lepoutre and Kate Hollinshead and Christian Ludwig and Melanie Menara and Aurelie Morin and Luis-Jaime Castro-Vega and Parker, {Seth J.} and Maxime Janin and Cosimo Martinelli and Chris Ottolenghi and Christian Metallo and Anne-Paule Gimenez-Roqueplo and Judith Favier and Daniel Tennant",
year = "2015",
month = nov,
day = "2",
doi = "10.1038/ncomms9784",
language = "English",
volume = "6",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Springer",

}

RIS

TY - JOUR

T1 - Loss of succinate dehydrogenase activity results in dependency on pyruvate carboxylation for cellular anabolism

AU - Lussey-Lepoutre, Charlotte

AU - Hollinshead, Kate

AU - Ludwig, Christian

AU - Menara, Melanie

AU - Morin, Aurelie

AU - Castro-Vega, Luis-Jaime

AU - Parker, Seth J.

AU - Janin, Maxime

AU - Martinelli, Cosimo

AU - Ottolenghi, Chris

AU - Metallo, Christian

AU - Gimenez-Roqueplo, Anne-Paule

AU - Favier, Judith

AU - Tennant, Daniel

PY - 2015/11/2

Y1 - 2015/11/2

N2 - The tricarboxylic acid (TCA) cycle is a central metabolic pathway responsible for supplying reducing potential for oxidative phosphorylation and anabolic substrates for cell growth, repair and proliferation. As such, it might be considered as essential for the ongoing viability and proliferation of a cell or tissue. However, since the first report in 2000 of an inactivating mutation in the TCA cycle enzyme complex, succinate dehydrogenase (SDH) in paraganglioma (PGL), it has become clear that some cells and tissues are not only able to survive with a truncated TCA cycle, but they are also able to support the cell growth and proliferative phenotype observed in tumours. Here, we show that loss of SDH activity leads to changes in the metabolism of non-essential amino acids: in particular, we demonstrate that pyruvate carboxylase is essential to re-fill the depleted pool of aspartate in SDH-deficient cells. Our work demonstrates that the loss of SDH reduces the metabolic plasticity of cells, indicating vulnerabilities that can be targeted therapeutically.

AB - The tricarboxylic acid (TCA) cycle is a central metabolic pathway responsible for supplying reducing potential for oxidative phosphorylation and anabolic substrates for cell growth, repair and proliferation. As such, it might be considered as essential for the ongoing viability and proliferation of a cell or tissue. However, since the first report in 2000 of an inactivating mutation in the TCA cycle enzyme complex, succinate dehydrogenase (SDH) in paraganglioma (PGL), it has become clear that some cells and tissues are not only able to survive with a truncated TCA cycle, but they are also able to support the cell growth and proliferative phenotype observed in tumours. Here, we show that loss of SDH activity leads to changes in the metabolism of non-essential amino acids: in particular, we demonstrate that pyruvate carboxylase is essential to re-fill the depleted pool of aspartate in SDH-deficient cells. Our work demonstrates that the loss of SDH reduces the metabolic plasticity of cells, indicating vulnerabilities that can be targeted therapeutically.

U2 - 10.1038/ncomms9784

DO - 10.1038/ncomms9784

M3 - Article

VL - 6

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 8784

ER -