Nanoplastics exacerbate cadmium toxicity in Mytilus coruscus through bioenergetic exhaustion and tissue...

The combined pollution of nanoplastics (NPs) and heavy metals poses an emerging threat to marine ecosystems, yet the bioenergetic mechanisms underlying their synergistic toxicity remain poorly understood. Herein, we investigated the synergistic lethal effects of polystyrene nanoplastics (PS-NPs) and cadmium (Cd) on the thick-shelled mussel, Mytilus coruscus. Our results indicated that PS-NPs exacerbated Cd accumulation via the "Trojan Horse" effect, leading to the collapse of antioxidant defenses. Crucially, histopathological analysis revealed a distinct pathological transition ranging from defensive epithelial hyperplasia observed in single-stressor exposures to severe necrotic desquamation and massive hemocytic infiltration in the combined exposure group, indicative of disintegration of the physical gill barrier. Mechanistically, this tissue collapse appeared to be driven by a severe energy supply-demand mismatch, characterized by the transcriptional suppression of the key gluconeogenic gene PEPCK and the failure to sustain compensatory ATP production. This relative energy deficit likely compromised ATP-dependent HSP-70 repair processes and the regulation of ordered apoptosis pathways, thereby shifting the mode of cell death toward uncontrolled necrosis and triggering a pronounced inflammatory response. This study proposes "bioenergetic uncoupling" as a critical mechanism underlying the shift from defense failure to tissue necrosis, providing novel mechanistic insights into the environmental risks of combined plastic pollution.