ArticleBioEssays : news and reviews in molecular, cellular and developmental biology2019
mTOR Senses Intracellular pH through Lysosome Dispersion from RHEB.
Article in BioEssays : news and reviews in molecular, cellular and developmental biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
5 citing papers in PubMed, 13 citations in OpenAlex.
- Circadian rhythms of macrophages are altered by the acidic tumor microenvironment.EMBO reports · 2024Article
- Intracellular acidification and glycolysis modulate inflammatory pathway in senescent cells.Journal of biochemistry · 2024Article
- Insulin Receptor Genetic Variants Causal Association with Type 2 Diabetes: A Mendelian Randomization Study.Current developments in nutrition · 2022Article
- Anti-cancer strategy targeting the energy metabolism of tumor cells surviving a low-nutrient acidic microenvironment.Molecular metabolism · 2020Article
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Authors and funding
3 authors at 2 institutions in 1 country.
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Abstract
Acidity, generated in hypoxia or hypermetabolic states, perturbs homeostasis and is a feature of solid tumors. That acid peripherally disperses lysosomes is a three-decade-old observation, yet one little understood or appreciated. However, recent work has recognized the inhibitory impact this spatial redistribution has on mechanistic target of rapamycin complex 1 (mTORC1), a key regulator of metabolism. This finding argues for a paradigm shift in localization of mTORC1 activator Ras homolog enriched in brain (RHEB), a conclusion several others have now independently reached. Thus, mTORC1, known to sense amino acids, mitogens, and energy to restrict biosynthesis to times of adequate resources, also senses pH and, via dampened mTOR-governed synthesis of clock proteins, regulates the circadian clock to achieve concerted responses to metabolic stress. While this may allow cancer to endure metabolic deprivation, immune cell mTOR signaling likewise exhibits pH sensitivity, suggesting that suppression of antitumor immune function by solid tumor acidity may additionally fuel cancers, an obstacle potentially reversible through therapeutic pH manipulation.
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