Thorium is a radioactive heavy metal and an emerging environmental pollutant. Ecological and human health risks from thorium exposure are growing with the excavation of rare earth metals and implementation of thorium-based nuclear reactors. Thorium poisoning is associated with carcinogenesis, liver impairments, and congenital anomalies. To date, the biomolecular targets that underlie thorium-induced toxicity remain unknown. Here, we used in vitro enzymatic activity assays to comprehensively evaluate the effects of thorium on the mitochondrial respiration process. Thorium was found to inhibit respiratory chain complex IV (cytochrome c oxidase) at sub-micromolar concentrations (IC₅₀ ~ 0.4 μM, 90 μg/L). This is lower than the thorium level limit (246 μg/L) in drinking water specified by the World Health Organization. The inhibitory effects were further verified in mitochondria from human bone and liver cells (thorium mainly deposits in these organs). The inhibition of cytochrome c oxidase can readily rationalize well-documented cellular toxicities of thorium, such as alteration of mitochondrial membrane potential and production of reactive oxygen species. Therefore, cytochrome c oxidase is potentially a key molecular target underlying thorium-induced toxicological effect.

钍是一种放射性重金属，是一种新兴的环境污染物。随着稀土金属的开采和钍基核反应堆的实施，钍暴露带来的生态和人类健康风险正在增加。钍中毒与致癌、肝损伤和先天性异常有关。迄今为止，钍诱导毒性的生物分子靶点仍然未知。在这里，我们使用体外酶活性测定来全面评估钍对线粒体呼吸过程的影响。钍被发现在亚微摩尔浓度（IC ₅₀~ 0.4 μM，90 μg/L）。这低于世界卫生组织规定的饮用水中钍含量限值（246 μg/L）。在人骨和肝细胞的线粒体中进一步证实了抑制作用（钍主要沉积在这些器官中）。细胞色素c氧化酶的抑制可以很容易地使钍的有据可查的细胞毒性合理化，例如线粒体膜电位的改变和活性氧的产生。因此，细胞色素c氧化酶可能是钍诱导毒理学作用的关键分子靶标。