Marine natural product aurilide activates the OPA1-mediated apoptosis by binding to prohibitin |
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Authors: | Sato Shin-ichi Murata Asako Orihara Tsubasa Shirakawa Takashi Suenaga Kiyotake Kigoshi Hideo Uesugi Motonari |
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Institution: | Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto 611-0011, Japan. |
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Abstract: | 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. |
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