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Glutamine‐fueled mitochondrial metabolism is decoupled from glycolysis in melanoma
Author(s) -
Filipp Fabian V.,
Ratnikov Boris,
De Ingeniis Jessica,
Smith Jeffrey W.,
Osterman Andrei L.,
Scott David A.
Publication year - 2012
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12000
Subject(s) - citric acid cycle , glutamine , glycolysis , biochemistry , glutaminolysis , serine , flux (metallurgy) , metabolism , alanine , amino acid , arginine , amino acid synthesis , metabolic network , biology , tricarboxylic acid , mitochondrion , chemistry , lysine , enzyme , organic chemistry
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.