Marine natural product aurilide activates the opa1-mediated apoptosis by binding to prohibitin

Shin Ichi Sato, Asako Murata, Tsubasa Orihara, Takashi Shirakawa, Kiyotake Suenaga, Hideo Kigoshi, Motonari Uesugi

Research output: Contribution to journalArticlepeer-review

74 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)131-139
Number of pages9
JournalChemistry and Biology
Volume18
Issue number1
DOIs
Publication statusPublished - 2011 Jan 28

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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