Flux-dependent increase in the stoichiometry of charge translocation by mitochondrial ATPase/ATP synthase induced by almitrine.
After studying the effects of almitrine, a new kind of ATPase/ATP synthase inhibitor, on two kinds of isolated mammalian mitochondrion, we have observed that: (1) Almitrine inhibits oligomycin-sensitive ATPase; it decreases the ATP/O value of oxidative phosphorylations without any change in the magnitude of delta mu H+. (2) Almitrine increases the mechanistic H+/ATP stoichiometry of ATPase as shown by measuring either (i) the extent of potassium acetate and of potassium phosphate accumulation sustained by ATP utilisation, or (ii) the electrical charge/ATP (K+/ATP) ratio at steady-state of ATPase activity. (3) Rat liver mitochondria are at least 10-times more sensitive to almitrine than beef heart mitochondria. (4) The change in H+/ATP stoichiometry induced by almitrine depends on the magnitude of the flux through ATPase. The inhibitory effect of almitrine on ATPase/ATP synthase complex, as a consequence of such an H+/ATP stoichiometry change, is discussed.
Rigoulet
M
M
Institut de Biochimie Cellulaire et Neurochimie du C.N.R.S., Université de Bordeaux, France.
Fraisse
L
L
Ouhabi
R
R
Guérin
B
B
Fontaine
E
E
Leverve
X
X
D000085:Acetates / Q000378:metabolism; D019342:Acetic Acid; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D015765:Almitrine / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000201:enzymology*; D008933:Mitochondrial Swelling / Q000187:drug effects; D009840:Oligomycins / Q000494:pharmacology; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010710:Phosphates / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D017680:Potassium Compounds; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011522:Protons; D051381:Rats; D011919:Rats, Inbred Strains; D014634:Valinomycin / Q000494:pharmacology
D000085:Acetates; D009840:Oligomycins; D010710:Phosphates; D017680:Potassium Compounds; D011522:Protons; D014634:Valinomycin; D000255:Adenosine Triphosphate; D015765:Almitrine; C013216:potassium phosphate; D000251:Adenosine Triphosphatases; D006180:Proton-Translocating ATPases; D019342:Acetic Acid; D011188:Potassium