![](/images/graphics-bg.png)
The Role of Mitochondrial NADPH-Dependent Isocitrate Dehydrogenase in Cancer Cells
Joint Authors
Source
International Journal of Cell Biology
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-05-20
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
Isocitrate dehydrogenase 2 (IDH2) is located in the mitochondrial matrix.
IDH2 acts in the forward Krebs cycle as an NADP+-consuming enzyme, providing NADPH for maintenance of the reduced glutathione and peroxiredoxin systems and for self-maintenance by reactivation of cystine-inactivated IDH2 by glutaredoxin 2.
In highly respiring cells, the resulting NAD+ accumulation then induces sirtuin-3-mediated activating IDH2 deacetylation, thus increasing its protective function.
Reductive carboxylation of 2-oxoglutarate by IDH2 (in the reverse Krebs cycle direction), which consumes NADPH, may follow glutaminolysis of glutamine to 2-oxoglutarate in cancer cells.
When the reverse aconitase reaction and citrate efflux are added, this overall “anoxic” glutaminolysis mode may help highly malignant tumors survive aglycemia during hypoxia.
Intermittent glycolysis would hypothetically be required to provide ATP.
When oxidative phosphorylation is dormant, this mode causes substantial oxidative stress.
Arg172 mutants of human IDH2—frequently found with similar mutants of cytosolic IDH1 in grade 2 and 3 gliomas, secondary glioblastomas, and acute myeloid leukemia—catalyze reductive carboxylation of 2-oxoglutarate and reduction to D-2-hydroxyglutarate, which strengthens the neoplastic phenotype by competitive inhibition of histone demethylation and 5-methylcytosine hydroxylation, leading to genome-wide histone and DNA methylation alternations.
D-2-hydroxyglutarate also interferes with proline hydroxylation and thus may stabilize hypoxia-induced factor α.
American Psychological Association (APA)
Smolková, Katarína& Ježek, Petr. 2012. The Role of Mitochondrial NADPH-Dependent Isocitrate Dehydrogenase in Cancer Cells. International Journal of Cell Biology،Vol. 2012, no. 2012, pp.1-12.
https://search.emarefa.net/detail/BIM-459424
Modern Language Association (MLA)
Smolková, Katarína& Ježek, Petr. The Role of Mitochondrial NADPH-Dependent Isocitrate Dehydrogenase in Cancer Cells. International Journal of Cell Biology No. 2012 (2012), pp.1-12.
https://search.emarefa.net/detail/BIM-459424
American Medical Association (AMA)
Smolková, Katarína& Ježek, Petr. The Role of Mitochondrial NADPH-Dependent Isocitrate Dehydrogenase in Cancer Cells. International Journal of Cell Biology. 2012. Vol. 2012, no. 2012, pp.1-12.
https://search.emarefa.net/detail/BIM-459424
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-459424