哺乳动物产生环八硫以抑制脂质过氧化和铁死亡
Mammals produce cyclo-octasulfur to suppress lipid peroxidation and ferroptosis
元素硫是古老的代谢物,但动物体内是否自身产生、储存在哪里、有什么作用一直不清楚。研究者发现哺乳动物体内存在最稳定的硫同素异形体——环八硫(S8),在细胞线粒体膜和脂滴中可积累到毫摩尔浓度。他们还鉴定出脂滴相关的一氧化氮合酶是S8的合成来源。S8在脂滴中积累能限制脂质过氧化、抑制铁死亡(一种依赖铁的细胞死亡方式)。在小鼠骨关节炎模型中,关节腔注射溶解态S8可减轻脂质过氧化。这提示S8是哺乳动物内源性的抗氧化保护机制。
为什么推荐给您:首次揭示哺乳动物内源环八硫的合成与抗铁死亡功能,属重要新机制。
不需要生物学背景,多打比方
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摘要Abstract
Elemental sulfur is an evolutionarily ancient metabolite, yet its generation, storage, and function in animals have remained unclear. We show that mammals harbor elemental sulfur in the form of its most stable allotrope, cyclo-octasulfur (S8). We found that S8 accumulates to millimolar concentrations in mitochondrial membranes and in lipid droplets in both mouse and human cells. We further identified lipid droplet-associated nitric oxide synthase as a source of S8 biosynthesis and found that S8 accumulation in lipid droplets limits lipid peroxidation and suppresses ferroptosis. Accordingly, intra-articular injection of solubilized S8 reduces lipid peroxidation in a mouse model of osteoarthritis. Together, these findings reveal an endogenous pool of S8 in mammals that may protect cells from oxidative membrane damage by modulating cellular sensitivity to ferroptosis.