Promyelocytic leukemia (PML) nuclear bodies (NBs) recruit partner proteins, including p53 and its regulators, thereby controlling their abundance or function. Investigating arsenic sensitivity of acute promyelocytic leukemia, we proposed that PML oxidation promotes NB biogenesis. However, physiological links between PML and oxidative stress response in vivo remain unexplored. Here, we identify PML as a reactive oxygen species (ROS) sensor. Pml^−/− cells accumulate ROS, whereas PML expression decreases ROS levels. Unexpectedly, Pml^−/− embryos survive acute glutathione depletion. Moreover, Pml^−/− animals are resistant to acetaminophen hepatotoxicity or fasting-induced steatosis. Molecularly, Pml^−/− animals fail to properly activate oxidative stress–responsive p53 targets, whereas the NRF2 response is amplified and accelerated. Finally, in an oxidative stress–prone background, Pml^−/− animals display a longevity phenotype, likely reflecting decreased basal p53 activation. Thus, similar to p53, PML exerts basal antioxidant properties but also drives oxidative stress–induced changes in cell survival/proliferation or metabolism in vivo. Through NB biogenesis, PML therefore couples ROS sensing to p53 responses, shedding a new light on the role of PML in senescence or stem cell biology.

早幼粒细胞白血病（PML）核体（NBs）募集伴侣蛋白，包括p53及其调节剂，从而控制其丰度或功能。调查急性早幼粒细胞白血病的砷敏感性，我们提出PML氧化促进NB生物发生。但是，在体内PML和氧化应激反应之间的生理联系仍待探索。在这里，我们将PML识别为活性氧（ROS）传感器。Pml ^-/-细胞积累ROS，而PML表达降低ROS水平。出乎意料的是，Pml ^-/-胚胎能在急性谷胱甘肽耗竭后存活。此外，Pml ^-/-动物对乙酰氨基酚的肝毒性或禁食诱导的脂肪变性有抵抗力。在分子上，Pml ^-/-动物无法正确激活氧化应激反应性p53靶标，而NRF2反应被放大并加速。最后，在容易产生氧化应激的背景下，Pml ^-/-动物表现出长寿的表型，可能反映了基础p53激活减少。因此，与p53相似，PML具有基本的抗氧化特性，而且还可以驱动体内氧化应激诱导的细胞存活/增殖或代谢变化。因此，通过NB生物发生，PML将ROS传感与p53反应耦合，从而使PML在衰老或干细胞生物学中的作用有了新的发现。