Sato Shin-ichi, Murata Asako, Orihara Tsubasa, Shirakawa Takashi, Suenaga Kiyotake, Kigoshi Hideo, Uesugi Motonari
Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto 611-0011, Japan.
Chem Biol. 2011 Jan 28;18(1):131-9. doi: 10.1016/j.chembiol.2010.10.017.
Aurilide is a potent cytotoxic marine natural product that induces apoptosis in cultured human cells at the picomolar to nanomolar range; however, its mechanism of action has been unknown. Results of the present study showed that aurilide selectively binds to prohibitin 1 (PHB1) in the mitochondria, activating the proteolytic processing of optic atrophy 1 (OPA1) and resulting in mitochondria-induced apoptosis. The mechanism of aurilide cytotoxicity suggests that PHB1 is an apoptosis-regulating protein amenable to modulation by small molecules. Aurilide may serve as a small-molecule tool for studies of mitochondria-induced apoptosis.
奥瑞利德是一种强效的细胞毒性海洋天然产物，在皮摩尔到纳摩尔范围内可诱导培养的人类细胞发生凋亡；然而，其作用机制一直未知。本研究结果表明，奥瑞利德选择性地与线粒体中的 prohibitin 1（PHB1）结合，激活视神经萎缩蛋白 1（OPA1）的蛋白水解加工，从而导致线粒体诱导的凋亡。奥瑞利德的细胞毒性机制表明，PHB1 是一种可被小分子调节的凋亡调节蛋白。奥瑞利德可作为研究线粒体诱导凋亡的小分子工具。
