Abstract
Every cell in the body is exposed to a certain level of CO(2) and O(2). Hypercapnia and hypoxia elicit stress signals to influence cellular metabolism and function. Both conditions exert profound yet distinct effects on metabolic pathways and mitochondrial dynamics, highlighting the need for cells to adapt to changes in the gaseous microenvironment. The interplay between hypercapnia and hypoxia signaling is the key for dictating cellular homeostasis as microenvironmental CO(2) and O(2) levels are inextricably linked. Hypercapnia, characterized by elevated pCO(2), introduces metabolic adaptations within the aerobic metabolism pathways, affecting tricarboxylic acid cycle flux, lipid, and amino acid metabolism, oxidative phosphorylation and the electron transport chain. Hypoxia, defined by reduced oxygen availability, necessitates a shift from oxidative phosphorylation to anaerobic glycolysis to sustain ATP production, a process orchestrated by the stabilization of hypoxia-inducible factor-1α. Given that hypoxia and hypercapnia are present in both physiological and cancerous microenvironments, how might the coexistence of hypercapnia and hypoxia influence metabolic pathways and cellular function in physiological niches and the tumor microenvironment?