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

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 c...

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Bibliographic Details
Published in:The international journal of biochemistry & cell biology 2008, Vol.40 (12), p.2698-2701
Main Authors: Grover, Gary J, Marone, Palma Ann, Koetzner, Lee, Seto-Young, Donna
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - chemistry
Adenosine Triphosphate - metabolism
Adenosine Triphosphate - pharmacology
Animals
Aurovertins - metabolism
Aurovertins - pharmacology
Enzyme Inhibitors - pharmacology
Forecasting
Humans
Hydrolysis
Imidazoles - pharmacology
Mitochondria - enzymology
Mitochondria - metabolism
Mitochondrial Proton-Translocating ATPases - antagonists & inhibitors
Mitochondrial Proton-Translocating ATPases - chemistry
Mitochondrial Proton-Translocating ATPases - metabolism
Models, Biological
Myocardial Ischemia - metabolism
Oligomycins - metabolism
Oligomycins - pharmacology
Signal Transduction
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Summary: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.
ISSN:1357-2725
DOI:10.1016/j.biocel.2008.06.013