Nanopollutants (nZnO) amplify hypoxia-induced cellular stress in a keystone marine bivalve, Mytilus edulis

Zinc oxide nanoparticles (nZnO) are increasingly utilized in industrial, medical, and personal care products, particularly as the main ingredient in sunscreens, raising concerns about their environmental impact, especially in coastal ecosystems. The Baltic Sea, experiencing severe eutrophication, faces persistent hypoxia due to excessive nutrient runoff and limited water exchange. Simultaneously, coastal pollution from industrial and urban activities introduces nZnO, a highly biotoxic nanopollutant. The combined effects of hypoxia and nZnO contamination may amplify environmental stress, yet their interactions remain insufficiently studied. This study investigates the combined effects of nZnO exposure and fluctuating dissolved oxygen regimes (specifically short- and long-term hypoxia and subsequent reoxygenation) on Mytilus edulis, a sentinel species in these ecosystems. By assessing a range of cellular and molecular markers, including oxidative stress, oxygen sensing, protein quality control, stress response, apoptosis, and inflammation, we show that nZnO exacerbates hypoxia-induced oxidative stress, delaying redox recovery and prolonging oxidative damage during reoxygenation. Specifically, nZnO exposure maintains elevated LPO and PC levels after reoxygenation, indicating prolonged oxidative imbalance. While M. edulis typically recovers from hypoxia-induced stress, nZnO disrupts this process by impairing antioxidant defenses, prolonging HIF-1α activation, and dysregulating p53, JNK, and p38 expression, thereby interfering with normal hypoxia-reoxygenation response. Additionally, nZnO alters HSP70, Lon protease, and caspase-3 regulation, disrupting protein-folding and apoptotic pathways. These findings suggest a synergistic interaction between nZnO and hypoxia, heightening the organism's vulnerability to environmental stress and suggesting risks for marine organisms in nanoparticle-polluted, hypoxia-prone coastal regions.