Abstract / Description of output
supply and demand. Here we show that MYC elevates global transcription and translation, even in the absence of glutamine, revealing metabolic demand without corresponding supply. Glutamine withdrawal from MRC-5 fibroblasts depletes key tricarboxylic acid (TCA) cycle metabolites and, in combination with MYC activation, leads to AMP accumulation and nucleotide catabolism indicative of energetic stress. Further analyses reveal that glutamine supports viability
through TCA cycle energetics rather than asparagine biosynthesis and that TCA cycle inhibition confers tumour suppression on MYC-driven lymphoma in vivo. In summary, glutamine supports the viability of MYC-overexpressing cells through an energetic rather than a biosynthetic mechanism.
Keywords / Materials (for Non-textual outputs)
- adenylate kinase
- nucleotide catabolism,
- nucleotide biosynthesis
- pentose phosphate pathway
- metabolic fix
FingerprintDive into the research topics of 'Myc sensitises cells to apoptosis by driving energetic demand'. Together they form a unique fingerprint.
Alex Von Kriegsheim (Manager)Deanery of Molecular, Genetic and Population Health Sciences