title: Marine natural product aurilide activates the OPA1-mediated apoptosis by binding to prohibitin.
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.
authors.affiliation: Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto 611-0011, Japan.
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Sato
authors.forename: Asako
authors.initials: A
authors.lastname: Murata
authors.forename: Tsubasa
authors.initials: T
authors.lastname: Orihara
authors.forename: Takashi
authors.initials: T
authors.lastname: Shirakawa
authors.forename: Kiyotake
authors.initials: K
authors.lastname: Suenaga
authors.forename: Hideo
authors.initials: H
authors.lastname: Kigoshi
authors.forename: Motonari
authors.initials: M
authors.lastname: Uesugi
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001688:Biological Products / Q000378:metabolism* / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D003603:Cytotoxins / Q000378:metabolism / Q000494:pharmacology; D047630:Depsipeptides / Q000378:metabolism* / Q000494:pharmacology*; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009792:Oceans and Seas; D000091402:Prohibitins; D011485:Protein Binding; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012097:Repressor Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D001688:Biological Products; D003603:Cytotoxins; D047630:Depsipeptides; C000717328:PHB protein, human; D000091402:Prohibitins; D012097:Repressor Proteins; C532913:aurilide; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human