Scopus Publication Detail
The publication detail shows the title, authors (with indicators showing other profiled authors), information on the publishing organization, abstract and a link to the article in Scopus. This abstract is what is used to create the fingerprint of the publication.
Oxidation of alpha-ketoglutarate is required for reductive carboxylation in cancer cells with mitochondrial defectsRalph J DeBerardinis; Zoltan Kovacs; Dinesh Rakheja)
Cell Reports. 2014;7(5):1679-1690.Abstract
Mammalian cells generate citrate by decarboxylating pyruvate in the mitochondria to supply the tricarboxylic acid (TCA) cycle. In contrast, hypoxia and other impairments of mitochondrial function induce an alternative pathway that produces citrate by reductively carboxylating α-ketoglutarate (AKG) via NADPH-dependent isocitrate dehydrogenase (IDH). It is unknown how cells generate reducing equivalents necessary to supply reductive carboxylation in the setting of mitochondrial impairment. Here, weidentified shared metabolic features in cells using reductive carboxylation. Paradoxically, reductive carboxylation was accompanied by concomitant AKG oxidation in the TCA cycle. Inhibiting AKG oxidation decreased reducing equivalent availability and suppressed reductive carboxylation. Interrupting transfer of reducing equivalents from NADH to NADPH by nicotinamide nucleotide transhydrogenase increased NADH abundance and decreased NADPH abundance while suppressing reductive carboxylation. The data demonstrate that reductive carboxylation requires bidirectional AKG metabolism along oxidative and reductive pathways, with the oxidative pathway producing reducing equivalents used to operate IDH in reverse. © 2014 The Authors.
This section shows information related to the publication - computed using the fingerprint of the publication - including related publications, related experts with fingerprints representing significant amounts of overlap between their fingerprint and this publication. The red dots indicate whether those experts or terms appear within the publication, thereby showing potential and actual connections.
Andrew R. Mullen; William W. Wheaton; Eunsook S. Jin; Pei-Hsuan Chen; Lucas B. Sullivan; Tzuling Cheng; Youfeng Yang; W. Marston Linehan; Navdeep S. Chandel; Ralph J. DeberardinisNature. 2012;481(7381):385-388.
I. Corbin; R. Simcoff; M. Novak; B.J. BlackburnParasitology Research. 1998;84(6):516-518.
Sarah M. Ronnebaum; Olga Ilkayeva; Shawn C. Burgess; Jamie W. Joseph; Danhong Lu; Robert D. Stevens; Thomas C. Becker; A. Dean Sherry; Christopher B. Newgard; Mette V. JensenJournal of Biological Chemistry. 2006;281(41):30593-30602.
Appears in this Document