Glutamine-fueled mitochondrial metabolism is decoupled from glycolysis in melanoma

Summary In this perspective, we revise the historic notion that cancer is a disease of mitochondria. We summarize recent findings on the function and rewiring of central carbon metabolism in melanoma. Metabolic profiling studies using stable isotope tracers show that glycolysis is decoupled from the...

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Bibliographic Details
Published in:Pigment cell and melanoma research 2012-11, Vol.25 (6), p.732-739
Main Authors: Filipp, Fabian V., Ratnikov, Boris, De Ingeniis, Jessica, Smith, Jeffrey W., Osterman, Andrei L., Scott, David A.
Format: Article
Language:English
Subjects:
Citric Acid Cycle
glutamine
Glutamine - metabolism
Glycolysis
Humans
Melanoma - metabolism
metabolism
mitochondria
Mitochondria - metabolism
NMR
Skin Neoplasms - metabolism
systems biology
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Summary:Summary In this perspective, we revise the historic notion that cancer is a disease of mitochondria. We summarize recent findings on the function and rewiring of central carbon metabolism in melanoma. Metabolic profiling studies using stable isotope tracers show that glycolysis is decoupled from the tricarboxylic acid (TCA) cycle. This decoupling is not ‘dysfunction’ but rather an alternate wiring required by tumor cells to remain metabolically versatile. In large part, this requirement is met by glutamine feeding the TCA cycle as an alternative source of carbon. Glutamine is also used in non‐conventional ways, like traveling in reverse through the TCA flux to feed fatty acid biosynthesis. Biosynthetic networks linked with non‐essential amino acids alanine, serine, arginine, and proline are also significantly impacted by the use of glutamine as an alternate carbon source.
ISSN:1755-1471
1755-148X
DOI:10.1111/pcmr.12000