Marine Natural Product Aurilide Activates the OPA1-Mediated Apoptosis by Binding to Prohibitin

作者：Sato Shin ichi; Murata Asako; Orihara Tsubasa; Shirakawa Takashi; Suenaga Kiyotake; Kigoshi Hideo; Uesugi Motonari^*

来源：Chemistry & Biology, 2011, 18(1): 131-139.

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.

• 出版日期2011-1-28