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 journalArticle

69 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

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Biological Products
Mitochondria
Apoptosis
Autosomal Dominant Optic Atrophy
Molecules
Cytotoxicity
Cultured Cells
Optics
Cells
Modulation
prohibitin
aurilide
Processing
Proteins

ASJC Scopus subject areas

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

Cite this

Marine natural product aurilide activates the opa1-mediated apoptosis by binding to prohibitin. / Sato, Shin Ichi; Murata, Asako; Orihara, Tsubasa; Shirakawa, Takashi; Suenaga, Kiyotake; Kigoshi, Hideo; Uesugi, Motonari.

In: Chemistry and Biology, Vol. 18, No. 1, 28.01.2011, p. 131-139.

Research output: Contribution to journalArticle

Sato, Shin Ichi ; Murata, Asako ; Orihara, Tsubasa ; Shirakawa, Takashi ; Suenaga, Kiyotake ; Kigoshi, Hideo ; Uesugi, Motonari. / Marine natural product aurilide activates the opa1-mediated apoptosis by binding to prohibitin. In: Chemistry and Biology. 2011 ; Vol. 18, No. 1. pp. 131-139.
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