A recent paper shows that under conditions of energy stress (the absence of glucose), aside from regulating ATP levels, AMP kinase (AMPK) activation inhibits the acetyl CoA carboxylases ACC1 and ACC2, preventing fatty acid synthesis (which requires NADPH), and promotes fatty acid oxidation (which produces NADPH). Knockdown of ACC enzymes promotes tumour formation in vivo, whereas ACC activation suppresses it. The conservation of NADPH levels is required to enable redox reactions that control the levels of reactive oxygen species, which are increased by metabolic stress.
ORIGINAL RESEARCH PAPER
Jeon, S.-M., Chandel, N. S. & Hay, N. AMPK regulates NADPH homeostasis to promote tumour cell survival during energy stress. Nature 9 May 2012 (doi:10.1038/nature11066)
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McCarthy, N. In need of a NADPH rush?. Nat Rev Cancer 12, 374 (2012). https://doi.org/10.1038/nrc3294
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DOI: https://doi.org/10.1038/nrc3294