The regulation of cell metabolism by hypoxia and hypercapnia.
Level 5 - mechanism / opinion, no new human data
Narrative review of cellular mechanisms without systematic methodology
PubMed 39914740 · doi:10.1016/j.jbc.2025.108252
What was done
This narrative review summarizes cellular and metabolic adaptations to changes in the gaseous microenvironment, specifically focusing on the distinct and overlapping metabolic signaling pathways regulated by hypoxia and hypercapnia in physiological tissues and the tumor microenvironment.
What was found
The abstract provides a qualitative mechanistic overview and reports no quantitative numbers or empirical data. It notes that hypercapnia (elevated pCO2) alters aerobic metabolic pathways including the tricarboxylic acid cycle, lipid and amino acid metabolism, oxidative phosphorylation, and the electron transport chain, whereas hypoxia shifts metabolism from oxidative phosphorylation to anaerobic glycolysis via hypoxia-inducible factor-1α stabilization.
Why it matters
Understanding how cells simultaneously adapt to altered CO2 and O2 concentrations provides insight into metabolic regulation within physiological niches and specialized settings like the tumor microenvironment.
Limits
This is a narrative review with no original experimental data, quantitative metrics, or systematic search methodology reported in the abstract.
Cited by
- supports Hypoxia in an expanding tumor mass damages mitochondria, causing aggressive cancer cells to shift away from oxidative phosphorylation toward glycolysis relying on fermentable fuels like glucose and glutamine.