Metabolomic identification of the target of the filopodia protrusion inhibitor glucopiericidin A

Mitsuhiro Kitagawa, Satsuki Ikeda, Etsu Tashiro, Tomoyoshi Soga, Masaya Imoto

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Identifying the targets of bioactive compounds is a major challenge in chemical biological research. Here, we identified the functional target of the natural bioactive compound glucopiericidin A (GPA) through metabolomic analysis. We isolated GPA while screening microbial samples for a filopodia protrusion inhibitor. Interestingly, GPA alone did not inhibit filopodia protrusion, but synergistically inhibit protrusion with the mitochondrial respiration inhibitor, piericidin A (PA). These results suggested that GPA might inhibit glycolysis. Capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) provided strong evidence that GPA suppresses glycolysis by functionally targeting the glucose transporter. GPA may therefore serve as a glucose transporter chemical probe. Simultaneous inhibition of both glycolysis and mitochondrial respiration dramatically decreased intracellular ATP levels, indicating that GPA inhibits ATP-dependent filopodia protrusion with PA. Our results represent a challenge of molecular target identification using metabolomic analysis.

Original languageEnglish
Pages (from-to)989-998
Number of pages10
JournalChemistry and Biology
Volume17
Issue number9
DOIs
Publication statusPublished - 2010 Sep 24

Fingerprint

Pseudopodia
Metabolomics
Glycolysis
Facilitative Glucose Transport Proteins
Respiration
Adenosine Triphosphate
Capillary electrophoresis
Capillary Electrophoresis
glucopiericidin A
Mass spectrometry
Mass Spectrometry
Screening
Research

ASJC Scopus subject areas

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

Cite this

Metabolomic identification of the target of the filopodia protrusion inhibitor glucopiericidin A. / Kitagawa, Mitsuhiro; Ikeda, Satsuki; Tashiro, Etsu; Soga, Tomoyoshi; Imoto, Masaya.

In: Chemistry and Biology, Vol. 17, No. 9, 24.09.2010, p. 989-998.

Research output: Contribution to journalArticle

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