Mitochondrial formation of hydrogen peroxide is causally linked to the antimycin A-mediated prevention of tert-butylhydroperoxide-induced U937 cell death

FEBS Lett. 1998 Jul 17;431(2):245-9. doi: 10.1016/s0014-5793(98)00764-9.

Abstract

Antimycin A and 2-heptyl-4-hydroxyquinoline N-oxide (HQNO), both of which bind to the same site of complex III, prevented U937 cell killing promoted by tert-butylhydroperoxide (tB-OOH). This cytoprotection was not directly caused by inhibition of electron transport or reduced formation of tB-OOH-derived toxic species, but rather appeared to be the consequence of a mechanism involving mitochondrial formation of hydrogen peroxide. Ubisemiquinone was most likely the electron donor allowing the formation of superoxides and, as a consequence, of hydrogen peroxide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Antimycin A / pharmacology*
  • Apoptosis / drug effects*
  • Cytochrome P-450 Enzyme Inhibitors
  • Drug Interactions
  • Electron Transport Complex III / antagonists & inhibitors
  • Humans
  • Hydrogen Peroxide / metabolism*
  • Hydroxyquinolines / pharmacology
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Peroxides / antagonists & inhibitors
  • Peroxides / pharmacology*
  • Tumor Cells, Cultured
  • tert-Butylhydroperoxide

Substances

  • Anti-Bacterial Agents
  • Cytochrome P-450 Enzyme Inhibitors
  • Hydroxyquinolines
  • Peroxides
  • 2-(n-heptyl)-4-hydroxyquinoline N-oxide
  • Antimycin A
  • tert-Butylhydroperoxide
  • Hydrogen Peroxide
  • Electron Transport Complex III