Photoaged Microplastics Disrupt the Response of Marine Medaka ( <i>Oryzias melastigma</i> ) to Ocean Acidification: Perspectives from Energy Metabolism and Ammonia Production

Ocean acidification (OA) and microplastics (MPs, <5 mm) are co-occurring stressors that threaten marine ecosystems. Although the marine environment contains multiple pollutants, OA can alter the environmental behavior of MPs, influencing their toxicity and environmental fate. Therefore, investigating the interactive effects of OA and MPs is essential. Fish can activate physiological compensatory mechanisms to adapt to OA; however, it remains unclear how MPs affect these mechanisms. In this study, marine medaka were exposed to acidified seawater (pH 7.70) containing environmentally relevant concentrations of MPs (0.1 mg/L) for 90 days to investigate the disruptive effects of MPs on responses to OA. The results showed that while OA triggered compensatory energy metabolism reprogramming to enhance ammonia production, MPs disrupted this process, reducing the TCA cycle intermediate α-ketoglutarate. This α-ketoglutarate deficiency limited the glutamate supply for ammonia production. Simultaneous inhibition of glutamate dehydrogenase activity further limited glutamate availability. As a result, MPs reduced the level of ammonia production by 25.29%, compromising the ability to neutralize excess H + . Crucially, photoaging exacerbated this toxicity, leading to a 32.04% reduction in ammonia production. This study demonstrates that MPs interfere with fish responses to OA via α-ketoglutarate-mediated metabolic reprogramming, highlighting a vulnerability in marine organisms facing climate change scenarios.