Loss of RBF1 changes glutamine catabolism

• DOI: 10.1101/gad.206227.112
• Publication Date: 2013-01-16T05:03:30Z
• Authors: Brandon N. Nicolay; Paulo A. Gameiro; Katrin Tschöp; Michael Korenjak; Andreas M. Heilmann; John M. Asara; Gregory Stephanop...; Othon Iliopoulos; Nicholas J. Dyson
• Keywords: Catabolism

Inactivation of the retinoblastoma tumor suppressor (pRB) alters expression a myriad genes. To understand altered cellular environment that these changes create, we took advantage Drosophila model system and used targeted liquid chromatography tandem mass spectrometry (LC-MS/MS) to profile metabolic occur when RBF1, fly ortholog pRB, is removed. We show RBF1-depleted tissues larvae are sensitive fasting. Depletion RBF1 causes major in nucleotide synthesis glutathione metabolism. Under fasting conditions, interconnect, increased replication demand associated with depletion pools. In vivo 13 C isotopic tracer analysis shows increase flux glutamine toward synthesis, presumably minimize oxidative stress. Concordantly, H 2 O preferentially promoted apoptosis tissues, sensitivity animals was specifically suppressed by either supplement or antioxidant N-acetyl-cysteine. Effects pRB activation/inactivation on catabolism were also detected human cell lines. These results inactivation RB proteins reprogramming consequences RBF/RB function present both flies