Phosphocholine-induced energy source shift alleviates mitochondrial dysfunction in lung cells caused by geospecific PM_2.5 components.

Abstract

Fine particulate matter (PM_2.5) is globally recognized for its adverse implications on human health. Yet, remain limited the individual contribution of particular PM_2.5 components to its toxicity, especially considering regional disparities. Moreover, prevention solutions for PM_2.5-associated health effects are scarce. In the present study, we comprehensively characterized and compared the primary PM_2.5 constituents and their altered metabolites from two locations: Taiyuan and Guangzhou. Analysis of year-long PM_2.5 samples revealed 84 major components, encompassing organic carbon, elemental carbon, ions, metals, and organic chemicals. PM_2.5 from Taiyuan exhibited higher contamination, associated health risks, dithiothreitol activity, and cytotoxicities than Guangzhou's counterpart. Applying metabolomics, BEAS-2B lung cells exposed to PM_2.5 from both cities were screened for significant alterations. A correlation analysis revealed the metabolites altered by PM_2.5 and the critical toxic PM_2.5 components in both regions. Among the PM_2.5-down-regulated metabolites, phosphocholine emerged as a promising intervention for PM_2.5 cytotoxicities. Its supplementation effectively attenuated PM_2.5-induced energy metabolism disorder and cell death via activating fatty acid oxidation and inhibiting <i>Phospho1</i> expression. The highlighted toxic chemicals displayed combined toxicities, potentially counteracted by phosphocholine. Our study offered a promising functional metabolite to alleviate PM_2.5-induced cellular disorder and provided insights into the geo-based variability in toxic PM_2.5 components.