Energetic signalling in the control of mitochondrial F1F0 ATP synthase activity in health and disease.
Int J Biochem Cell Biol
; 40(12): 2698-701, 2008.
Article
em En
| MEDLINE
| ID: mdl-18707016
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Trifosfato de Adenosina
/
ATPases Mitocondriais Próton-Translocadoras
/
Mitocôndrias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Int J Biochem Cell Biol
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos