A Closed Computational-Experimental Loop Identifies Metabolic Collapse at the Root of Macrophage Dysfunction due to Zinc Dyshomeostasis.

ABSTRACT: Zinc plays a crucial role in immune regulation, the oxidative stress response, and epithelial barrier integrity, yet zinc's precise role in regulating metabolic and immunological functions in myeloid cells remains poorly understood. Here, we employ a systems biology approach using constraint-based modeling to elucidate the consequences of myeloid-specific loss of ZIP8 on macrophage metabolic function and antibacterial capabilities. We demonstrate that macrophage populations in the lung of ZIP8 knockout (Zip8KO) mice exhibit widespread metabolic disruption, spanning glycolysis, butanoate metabolism, amino acid metabolism, and mitochondrial function. Specifically, Zip8KO macrophages exhibit impaired nutrient uptake and dysregulated energy metabolism, which is exacerbated follow

SUBMITTER: Malla S 

PROVIDER: S-EPMC12803191 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature