Polystyrene microplastics disrupt osteogenic differentiation via lysosome-mediated mitochondrial dysfunction: Protective role of mTOR signaling
Year: 2025
Type: article
Abstract: Polystyrene microplastics (PS-MPs), increasingly detected in aquatic environments, raise health concerns for humans and animals. However, their specific cellular effects remain incompletely characterized. This study identifies a mechanistic pathway by which PS-MPs impair osteogenic differentiation via organelle-specific stress responses in zebrafish larvae and MC3T3-E1 preosteoblasts. PS-MP exposure delayed vertebral mineralization and downregulation of key osteogenic makers. Mechanistically, PS-MPs were internalized through clathrin-mediated endocytosis, transported via the endo -lysosomal system, and accumulated within lysosomes. Lysosomal accumulation of PS-MPs induced lysosomal membrane permeabilization, indicated by increaed colocalization of galectin-3 and lysosomeassociated membrane protein 1, leading to oxidative stress. The resulting mitochondrial dysfunction included initial compensatory fusion responses, followed by impaired mitochondrial dynamics and suppressed mitochondrial biogenesis. These effects were accompanied by activation of PTEN-induced kinase 1/Parkin-mediated mitophagy and exacerbated lysomal stress. Notably, pharmacological activation of mammalian target of rapamycin (mTOR) signaling with MHY1485 restored mitochondrial abundance, upregulated peroxisome proliferator-activated receptor gamma coactivator 1-alpha, reduced mitophagy, and stabilized lysomal membrane integrity–without altering PS-MP uptake. Collectively, these findings reveal a novel organelle-to-organelle stress axis initiated by PS-MP exposure and suggest mTOR activation as a potential therapeutic approach to mitigate PS-MP-induced cellular dysfunction.
Language: English
Subfield: Pollution
Field: Environmental Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $700
Awards: G5640577383, G6122417209
OpenAlex ID: W4417098038
