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.

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At a glance

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 type	5 - Mechanistic / In Vitro
Model system	Human cells; xenograft tumors
Journal	Molecular Cell
Year	2022
Peer reviewed	Yes
Record last updated	2026-09-23
Source	DOI 10.1016/j.molcel.2022.06.008 · PMID 35772404 · Free full text (PMC9444906)

Extracted findings

Intervention	Genetic (SLC4A7 loss); mTORC1 modulation
Target	mTORC1 / S6K / eIF4B / SLC4A7 (NBCn1)
Model	Human cells; mouse xenograft tumors
Effect	mTORC1 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}
}