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Pigment Cell Melanoma Res. 2012 Nov;25(6):732-9. doi: 10.1111/pcmr.12000. Epub 2012 Oct 1.

Glutamine-fueled mitochondrial metabolism is decoupled from glycolysis in melanoma.

Author information

1
Cancer Research Center, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA. filipp@ucmerced.edu

Abstract

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.

PMID:
22846158
PMCID:
PMC3639292
DOI:
10.1111/pcmr.12000
[Indexed for MEDLINE]
Free PMC Article
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