Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of α-ketoglutarate to citrate to support cell growth and viability

By David R. Wise, Patrick S. Ward, Jessica E. S. Shay, J. Cross, J. Gruber, U. Sachdeva, Jesse M. Platt, Raymond G Dematteo, M. C. Simon, Craig B. Thompson. Proceedings of the National Academy of Sciences of the United States of America, 2011

984 citations recorded by the source corpus.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/feed9a813fc6a8b873d4bea14e34cd83eecca140

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. Ralph J. Deberardinis
2. Craig B. Thompson
3. Guido Kroemer
4. David M. Sabatini
5. G. Semenza
6. Erika L. Pearce
7. Ping Gao
8. L. Galluzzi

In Molecular Biology

1. Guido Kroemer
2. Ralph J. Deberardinis
3. L. Galluzzi
4. Craig B. Thompson
5. David M. Sabatini
6. G. Semenza
7. J. Cantor
8. Erika L. Pearce

Citations in the corpus

• Metabolic regulation of epigenetics (2012, background): “Citrate produced from metabolism of glutamine in the TCA cycle can also contribute to the production of cytosolic acetyl-CoA (Metallo et al., 2012; Mullen et al., 2012; Wise et al., 2011).”
• HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations. (2013, positive): “The increased expression of BNIP3, LDHA, and PDK1 shunts pyruvate away from the mitochondria and reduces flux through the TCA pathway, the generation of NADH and FADH 2 that feed the electron transport chain, and thus ROS generation under hypoxic conditions.”
• An Integrated Metabolic Atlas of Clear Cell Renal Cell Carcinoma (2016, positive): “One of the key HIF1 targets in glycolysis is pyruvate dehydrogenase kinase, which phosphorylates and inhibits pyruvate dehydrogenase (PDH), thereby impeding fueling of pyruvate-derived carbons to the TCA cycle (Gordan et al., 2007; Kaelin, 2008; Semenza, 2013).”
• Mitochondrial metabolism and cancer (2017, background): “Alongside, mitochondria attracted renovated attention also from a metabolic perspective, in particular as it became clear that: (1) some mitochondrial metabolites are sufficient to drive oncogenesis [22], and (2) some mitochondrial circuitries can adapt to serve bioenergetic or anabolic functions, h”
• Hooked on fat: the role of lipid synthesis in cancer metabolism and tumour development (2013, background): “It has been shown that hypoxic cells use glutamine as a major substrate for lipid synthesis (Metallo et al., 2012; Wise et al., 2011).”
• Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate (2012, background): “In place of oxidative metabolism of both glucose and glutamine, these cancers preferentially perform reductive and carboxylating biosynthetic reactions from glutamine carbon (Le et al., 2012; Metallo et al., 2012; Mullen et al., 2012; Wise et al., 2011).”
• Glutamine oxidation maintains the TCA cycle and cell survival during impaired mitochondrial pyruvate transport (2014, background): “Reductive labeling of citrate from 13Cglutamine is enhanced when electron transport chain (ETC) or TCA cycle function is altered by hypoxia or mutations (Metallo et al., 2012; Mullen et al., 2012; Scott et al., 2011; Wise et al., 2011).”