mTORC1 induces purine synthesis through control of the mitochondrial tetrahydrofolate cycle

In response to growth signals, mechanistic target of rapamycin complex 1 (mTORC1) stimulates anabolic processes underlying cell growth. We found that mTORC1 increases metabolic flux through the de novo purine synthesis pathway in various mouse and human cells, thereby influencing the nucleotide pool available for nucleic acid synthesis. mTORC1 had transcriptional effects on multiple enzymes contributing to purine synthesis, with expression of the mitochondrial tetrahydrofolate (mTHF) cycle enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) being closely associated with mTORC1 signaling in both normal and cancer cells. MTHFD2 expression and purine synthesis were stimulated by activating transcription…

• NS
  National Science Foundation

  Award: DGE-1144152
• TS
  Tuberous Sclerosis Alliance
• LF
  LAM Foundation
• NI
  National Institutes of Health

  Awards: P01-CA120964, R35-CA197459, K99-CA194192, P30-CA006516, R01-CA181390