Hello, everyone. My question is basically the same as the title above. Are there instances of intracellular acidification resulting in an extremely low pH (excluding lysosomes)?
In 2023, Wei Li and Kosuke Kawaguchi group reported that, in senescence-induced breast cancer cells, ATP6AP2 expression is downregulated, leading to lysosomal dysfunction and a drastic drop in intracellular pH.
(Li, W., Kawaguchi, K., Tanaka, S., He, C., Maeshima, Y., Suzuki, E., & Toi, M. (2023). Cellular senescence triggers intracellular acidification and lysosomal pH alkalinized via ATP6AP2 attenuation in breast cancer cells. Communications Biology, 6, Article 1147. https://doi.org/10.1038/s42003-023-05482-7)
I’m curious to know whether there are other studies showing intracellular pH dropping to such extreme levels, aside from lysosomes and the extracellular environment. If you have any references or insights, please let me know!
Intracellular acidification can also be caused by lactate accumulation and mitochondrial dysfunction. Related pathways that can get affected are involved in regulation of cell metabolism, their survival and inflammation. Most sensitive pathways are AMPK, mTOR, NF-kB and PI3K/Akt. Studies have reported the role of reactive oxygen species stimulated by stress signal triggering inflammation "Defining roles of specific reactive oxygen species (ROS) in cell biology and physiology by Helmut Sies et al". In any of the cases, the disruption in proton gradient can destabilise the ions and cells internal pH drops drastically. This dysregulation contributes to pathological conditions like tumor progression as one mentioned in your question and even cellular senescence. Disturbance in lactate ions and proton gradient could acidify cytosol through events majorly involved in glycolysis.
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