Oliver's mTOR Atlas Evidence Platform
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The mTORC1-SLC4A7 axis stimulates bicarbonate import to enhance de novo nucleotide synthesis

Ali ES, Lipońska A, O'Hara BP, Amici DR, Torno MD, Gao P, Asara JM, Yap MF, Mendillo ML, Ben-Sahra I · 2022 · Molecular Cell · Atlas ID ALI2022

What this study shows

Building a nucleotide needs a carbon donor, and cells get it from bicarbonate dissolved in their surroundings. This study shows mTORC1 does not just switch on the nucleotide enzymes - it also arranges the delivery of the raw material. Through S6K and the translation factor eIF4B, mTORC1 selectively increases translation of the mRNA for SLC4A7, a sodium-bicarbonate cotransporter, so more bicarbonate is pulled into the cell. Removing SLC4A7 from cells with hyperactive mTORC1 cut flux through both de novo purine and pyrimidine synthesis and slowed cell and tumor growth, without changing intracellular pH - so the transporter matters as a supply line, not as a pH regulator. A fourth distinct route by which mTORC1 feeds nucleotide synthesis, alongside CAD (BEN2013), the mitochondrial folate cycle (BEN2016) and demand coupling (VAL2017).

Abstract

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Bicarbonate (HCO3-) ions maintain pH homeostasis in eukaryotic cells and serve as a carbonyl donor to support cellular metabolism. However, whether the abundance of HCO3- is regulated or harnessed to promote cell growth is unknown. The mechanistic target of rapamycin complex 1 (mTORC1) adjusts cellular metabolism to support biomass production and cell growth. We find that mTORC1 stimulates the intracellular transport of HCO3- to promote nucleotide synthesis through the selective translational regulation of the sodium bicarbonate cotransporter SLC4A7.

Read the full abstract on PubMed →

At a glance

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Evidence type M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Human cells; xenograft tumors) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type5 - Mechanistic / In Vitro
Model systemHuman cells; xenograft tumors
JournalMolecular Cell
Year2022
Peer reviewedYes
Record last updated2026-10-01
SourceDOI 10.1016/j.molcel.2022.06.008 · PMID 35772404 · Free full text (PMC9444906)

Where this study fits

How this study connects to the pathway map, open questions, people and other studies in the Atlas.

Pathway relations

Supports

mTORC1 activates Nucleotide synthesis

Strongest evidence: M (Molecular — cells, biochemistry, structure) · settled in the literature · Status: Proposed

plausible in people, not shown directly

Cancer cell and mammalian cell studies, including xenograft tumours (VAL2017, BEN2016, ALI2022). The evidence comes mostly from dividing or tumour cells; whether non-dividing tissues use the same route is not shown.

Supports

S6K1 activates Nucleotide synthesis

Strongest evidence: M (Molecular — cells, biochemistry, structure) · settled in the literature · Status: Proposed

plausible in people, not shown directly

Mammalian cell studies including xenograft tumours (BEN2013, ROB2013, ALI2022). The evidence comes from cultured and tumour cells; whether non-dividing tissues use the same route is not shown.

People in the Atlas

  • Eunus S. Ali first author · 3 studies in the Atlas

    Showed as a Ben-Sahra-lab postdoc that ERK2 directly activates the purine-synthesis enzyme PFAS, and that mTORC1 increases bicarbonate import through SLC4A7 to fuel nucleotide synthesis. His Kentucky lab studies how growth signals control nucleotide metabolism in cancer

  • Issam Ben-Sahra last author · 5 studies in the Atlas

    Showed as a postdoc in Brendan Manning's lab that mTORC1 drives both pyrimidine and purine synthesis, through two different mechanisms. His Northwestern lab has extended this to bicarbonate import, SAM synthesis and ERK control of purine production

  • Brendan P. O'Hara 3 studies in the Atlas

    As lab manager of Issam Ben-Sahra's lab at Northwestern, contributed to its studies of how mTORC1 and ERK control nucleotide synthesis, SAM production and bicarbonate import

  • Peng Gao 4 studies in the Atlas

    Directs the Northwestern metabolomics core that supplied mass-spectrometry metabolite measurements for three Ben-Sahra lab studies on how mTORC1 and ERK signalling drive nucleotide and SAM synthesis.

  • John M. Asara 9 studies in the Atlas

    Mass-spectrometry specialist whose core facility supplied metabolomics and proteomics for several mTOR studies, including measurements of purine, pyrimidine and SAM metabolism downstream of mTORC1.

More: 5 other authors

No profile yet: Lipońska A, Amici DR, Torno MD, Yap MF, Mendillo ML

Related studies

More related studies

All 212 studies on mTORC1

Topics

mTORC1Nucleotide synthesisS6K1

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

InterventionGenetic (SLC4A7 loss); mTORC1 modulation
TargetmTORC1 / S6K / eIF4B / SLC4A7 (NBCn1)
ModelHuman cells; mouse xenograft tumors
EffectmTORC1 raises SLC4A7 translation to import bicarbonate and sustain de novo purine and pyrimidine synthesis, cell growth and tumor growth

Cite this paper

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Ali, E. S., Lipońska, A., O'Hara, B. P., Amici, D. R., Torno, M. D., Gao, P., Asara, J. M., Yap, M. F., Mendillo, M. L., & Ben-Sahra, I. (2022). The mTORC1-SLC4A7 axis stimulates bicarbonate import to enhance de novo nucleotide synthesis. Molecular Cell. https://doi.org/10.1016/j.molcel.2022.06.008

@article{ALI2022,
  author       = {Ali, E. S. and Lipońska, A. and O'Hara, B. P. and Amici, D. R. and Torno, M. D. and Gao, P. and Asara, J. M. and Yap, M. F. and Mendillo, M. L. and Ben-Sahra, I.},
  title        = {{The mTORC1-SLC4A7 axis stimulates bicarbonate import to enhance de novo nucleotide synthesis}},
  journal      = {Molecular Cell},
  year         = {2022},
  doi          = {10.1016/j.molcel.2022.06.008},
  note         = {PMID: 35772404},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper. 

Barton, O. (2026). Oliver's mTOR Atlas (record ALI2022) [Data set]. https://mtor-atlas.org/study/ALI2022/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_ALI2022,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record ALI2022},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/ALI2022/},
  doi          = {10.5281/zenodo.22059963}
}
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