Mitochondrial dynamics in environmental neurotoxicity: beyond oxidative stress toward spatial and functional...

Environmental stressors are widely recognized as key drivers of neurotoxicity, yet their underlying mechanisms are still predominantly interpreted within a damage-centered framework focused on mitochondrial dysfunction, particularly oxidative stress and bioenergetic impairment.This perspective, primarily based on measurements of oxidative stress and bioenergetic impairment, cannot fully explain the spatial heterogeneity and selective vulnerability that define neuronal injury. Increasing evidence indicates that mitochondrial dynamics, including fission-fusion balance, intracellular transport, and quality control, function as an integrated regulatory system that actively organizes mitochondrial networks. Through the coordination of spatial distribution, functional renewal, and damage segregation, these processes shape how neurons respond to environmental challenges. Rather than serving as passive indicators of injury, mitochondrial dynamics determine whether cells maintain adaptive compensation or progress toward irreversible degeneration. In this review, we summarize how environmental stressors disrupt mitochondrial biology and propose mitochondrial dynamics as a central axis linking environmental exposure to neuronal fate. This perspective shifts the focus from static descriptions of dysfunction to dynamic regulation of mitochondrial networks and provides a conceptual framework for understanding heterogeneous neurotoxic outcomes while highlighting new opportunities for therapeutic intervention.