Energetic signalling in the control of mitochondrial F1F0 ATP synthase activity in health and disease

Gary J. Grover, Palma Ann Marone, Lee Koetzner, Donna Seto-Young

Research output: Contribution to journalShort surveypeer-review

26 Scopus citations

Abstract

The mitochondrial F1F0 ATP synthase is a critical enzyme that works by coupling the proton motive force generated by the electron transport chain via proton transfer through the F0 or proton-pore forming domain of this enzyme to release ATP from the catalytic F1 domain. This enzyme is regulated by calcium, ADP, and inorganic phosphate as well as increased transcription through several pathways. This enzyme is also an ATP hydrolase under ischemic conditions. This "inefficient" hydrolysis of ATP consumes 90% of ATP consumed during ischemia as shown with non-selective ATPase inhibitors oligomycin and Aurovertin B. A benzopyran analog, BMS-199264, selectively inhibits F1F0 ATP hydrolase activity with no effect on ATP synthase activity. BMS-199264 had no effect on ATP before ischemia, but reduced the decline in ATP during ischemia. Selective hydrolase inhibition seen with the small molecule BMS-199264 suggests a conformational change in the F1F0 ATPase enzyme when switching from synthase to hydrolase activity.

Original languageEnglish
Pages (from-to)2698-2701
Number of pages4
JournalInternational Journal of Biochemistry and Cell Biology
Volume40
Issue number12
DOIs
StatePublished - 2008
Externally publishedYes

Keywords

  • Adenosine triphosphate (ATP)
  • Aurovertin
  • BMS-199264
  • FF ATP hydrolase
  • Heart
  • Infarction
  • Mitochondria
  • Mitochondrial FF ATP synthase
  • Myocardial ischemia
  • Oligomycin
  • Reperfusion

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