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mTORC1 induces purine synthesis through control of the mitochondrial tetrahydrofolate cycle

2016; American Association for the Advancement of Science; Volume: 351; Issue: 6274 Linguagem: Inglês

10.1126/science.aad0489

1095-9203

Issam Ben‐Sahra, Gerta Hoxhaj, Stéphane J. H. Ricoult, John M. Asara, Brendan D. Manning,

Mitochondrial Function and Pathology

Controlling supplies for DNA and RNA synthesis The mTORC1 protein kinase complex regulates anabolic metabolism and coordinates cellular signals that promote growth with availability of required precursor metabolites. Signaling through mTORC1 controls pyrimidine synthesis. Ben-Sahra et al. found that mTORC1 also functions by a different mechanism to regulate purine biosynthesis, thus generating precursors for the synthesis of RNA and DNA (see the Perspective by Ma and Jones). Signaling by mTORC1 caused accumulation of the transcription factor ATF4, which enhances production of the enzyme methylenetetrahydrofolate dehydrogenase 2, thus leading to increased production of the purine nucleotides needed for cell growth. Science , this issue p. 728 ; see also p. 670