Polystyrene nanoplastics target electron transport chain complexes in brain mitochondria

Polystyrene nanoplastics (PS-NPs), derived from the breakdown of environmental plastics, have been detected in multiple tissues including the brain, raising concerns over their potential neurotoxicity. Mitochondrial dysfunction is a hallmark of neurodegenerative diseases, ageing, and exposure to classical neurotoxins and pesticides. In this study we investigated the effects of PS-NPs on mitochondrial function in both non-synaptic and synaptic mitochondria isolated from rat brains. Exposure to PS-NPs significantly reduced oxygen specifically impairing electron flow between complexes I–III, II–III and complex IV. Interestingly, individual activities of complex I or complex II were not significantly affected, suggesting that PS-NPs selectively disrupt electron transfer from complex I to complex III, or from complex II to complex III. Similar inhibition of electron flow between complexes I–III and II–III were identified in synaptic mitochondria, indicating the potential for nanoplastics to affect synaptic plasticity. Our findings reveal a mitochondrial mechanism of PS-NPs-induced neurotoxicity and highlight their potential contribution to brain energy metabolism deficits linked to environmental pollutants. Created in BioRender. • Polystyrene nanoplastics (PS-NPs) inhibit brain mitochondrial respiration. • PS-NPs impair both synaptic and non-synaptic mitochondrial complexes. • PS-NPs selectively impair electron transfer between complexes I–III and II–III. • Findings reveal a novel mechanism of PS-NP neurotoxicity relevant to exposure.