How Acidic Environments Affect mTORC1 Signaling
Author Information
Author(s): Balgi Aruna D., Diering Graham H., Donohue Elizabeth, Lam Karen K. Y., Fonseca Bruno D., Zimmerman Carla, Numata Masayuki, Roberge Michel
Primary Institution: University of British Columbia
Hypothesis
Can mTORC1 respond to changes in extracellular or cytoplasmic pH and limit anabolic processes in acidic conditions?
Conclusion
Acidic pH inhibits mTORC1 signaling, which may help cells adapt to metabolically stressful conditions.
Supporting Evidence
- Acidic pH rapidly inhibits mTORC1 signaling in MCF-7 cells.
- The TSC1–TSC2 complex is required for mTORC1 inhibition by acidic pH.
- mTORC1 activity returns to normal when pH is restored to physiological levels.
- Acidic pH affects upstream signaling pathways, particularly the Raf-MEK-ERK pathway.
Takeaway
When the environment around cells becomes too acidic, it can slow down their growth and energy use, helping them survive tough times.
Methodology
The study examined the effects of acidifying the extracellular medium on human breast carcinoma MCF-7 cells and mouse embryo fibroblasts, measuring mTORC1 activity through phosphorylation of its substrates.
Limitations
The study primarily focused on specific cell lines and may not generalize to all cell types or conditions.
Digital Object Identifier (DOI)
Want to read the original?
Access the complete publication on the publisher's website