Carbendazim Disrupts Cellular Homeostasis and Proteostasis in Caenorhabditis elegans: A Global Proteomic Approach
The extensive use of the broad-spectrum fungicide carbendazim (CBZ) has raised increasing environmental concerns due to its persistence and toxicity, leading to regulatory restrictions in several countries. Despite its widespread occurrence, the molecular mechanisms underlying CBZ toxicity in non-target organisms remain poorly understood. Here, we employed quantitative proteomics to characterize the systemic molecular response of Caenorhabditis elegans following exposure to a sublethal concentration of CBZ (0.01 mg.mL-1) from the L1 larval stage to day 1 of adulthood. A total of 273 differentially abundant proteins were identified in the N2 strain. Functional enrichment analysis revealed coordinated alterations in biological processes associated with protein synthesis, proteostasis, mitochondrial function, energy and lipid metabolism, intracellular trafficking, chromatin organization, and redox homeostasis, indicating extensive cellular reprogramming in response to CBZ exposure. Protein-protein interaction network analysis further identified ribosomal proteins and translation-associated factors as the principal hub proteins, suggesting that disruption of the translational machinery represents a central molecular event underlying CBZ toxicity. Collectively, these findings show that CBZ's biological effects extend beyond its established role as a microtubule-disrupting fungicide, affecting multiple interconnected cellular pathways involved in maintaining homeostasis. This study provides the first comprehensive proteomic characterization of CBZ toxicity in C. elegans, offering new mechanistic insights into its mode of action and highlighting the utility of integrative proteomics for assessing the impact of environmental contaminants on non-target organisms.