Caenorhabditis elegans as a Model System for Environmental Mitotoxicants

Environmental pollutants such as heavy metals, pesticides, and plastic nanoparticles pose significant risks to human, animal, and environmental health. New approach methodologies complying with the 3R principles (replace, reduce, refine) are essential for advancing the molecular basis of pollutant-induced toxicity, thus improving risk assessment, disease prevention, and therapies. Thanks to its remarkable features, the multicellular organism <i>Caenorhabditis elegans</i> offers unique opportunities to meet this goal. Mitochondria, central hubs in cellular homeostasis, are particularly vulnerable to pollutants, orchestrating stress responses that progress to toxicity and disease. <i>C. elegans</i> represents a powerful model to study these effects, offering conserved systems with quantifiable end points. While previous studies have mainly focused on environmental stressors inducing DNA damage, this review explores <i>C. elegans</i>'s end points of relevance for mitotoxicology, highlighting advantages and limitations of the system as an alternative approach for in vivo environmental-induced mitochondrial toxicology and diseases.