Pollutant-regulated mitophagy: new perspectives in environmental toxicology

Environmental pollutants such as heavy metals, pesticides, air pollutants, and industrial chemicals pose serious threats to human health, in part by disrupting mitochondrial function. Mitophagy, a selective autophagic process that eliminates impaired mitochondria, is essential for maintaining mitochondrial and cellular homeostasis. Recent studies have shown that various pollutants can impair or dysregulate mitophagy, particularly through pathways such as PTEN-induced kinase 1 (PINK1)/Parkin-mediated mechanisms, leading to mitochondrial dysfunction, oxidative stress, inflammation, and ultimately contributing to diseases including neurodegeneration, cancer, and metabolic disorders. This review comprehensively summarizes the mechanisms by which different classes of environmental pollutants regulate mitophagy, the molecular signaling pathways involved, and the downstream effects on cellular health. Furthermore, this review also discusses current drugs and natural interventions that can alleviate pollutant-induced mitophagy dysfunction, such as melatonin, resveratrol, selenium, and stem cell therapy. By integrating the latest advances in environmental toxicology and mitochondrial biology, the review offers novel perspectives on the role of mitophagy in pollutant toxicity and highlights promising strategies for mitigating the adverse health effects of environmental exposures.