Benzoquinone ansamycin 17AAG binds to mitochondrial voltage-dependent anion channel and inhibits cell invasion Academic Article uri icon


MeSH Major

  • Mitochondria
  • Voltage-Dependent Anion Channels


  • Geldanamycin and its derivative 17AAG [17-(Allylamino)-17-demethoxygeldanamycin, telatinib] bind selectively to the Hsp90 chaperone protein and inhibit its function. We discovered that these drugs associate with mitochondria, specifically to the mitochondrial membrane voltage-dependent anion channel (VDAC) via a hydrophobic interaction that is independent of HSP90. In vitro, 17AAG functions as a Ca(2+) mitochondrial regulator similar to benzoquinone-ubiquinones like Ub0. All of these compounds increase intracellular Ca(2+) and diminish the plasma membrane cationic current, inhibiting urokinase activity and cell invasion. In contrast, the HSP90 inhibitor radicicol, lacking a bezoquinone moiety, has no measurable effect on cationic current and is less effective in influencing intercellular Ca(2+) concentration. We conclude that some of the effects of 17-AAG and other ansamycins are due to their effects on VDAC and that this may play a role in their clinical activity.

publication date

  • March 8, 2011



  • Academic Article



  • eng

PubMed Central ID

  • PMC3053964

Digital Object Identifier (DOI)

  • 10.1073/pnas.1015181108

PubMed ID

  • 21368131

Additional Document Info

start page

  • 4105

end page

  • 10


  • 108


  • 10