The mitochondrial consequences of uncoupling intact cells depend on the nature of the exogenous substrate

In isolated mitochondria the consequences of oxidative phosphorylation uncoupling are well defined, whereas in intact cells various effects have been described. Uncoupling liver cells with 2,4-dinitrophenol (DNP) in the presence of dihydroxyacetone (DHA) and ethanol results in a marked decrease in m...

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Bibliographic Details
Published in:Biochemical journal 2001-04, Vol.355 (Pt 1), p.231-235
Main Authors: Sibille, B, Filippi, C, Piquet, M A, Leclercq, P, Fontaine, E, Ronot, X, Rigoulet, M, Leverve, X
Format: Article
Language:English
Subjects:
Adenosine Diphosphate
Adenosine Diphosphate - metabolism
Adenosine Triphosphate
Adenosine Triphosphate - metabolism
Animals
Cellular Biology
Life Sciences
Male
Mitochondria, Liver
Mitochondria, Liver - metabolism
Mitochondria, Liver - physiology
Oxidation-Reduction
Oxidative Phosphorylation
Oxygen Consumption
Rats
Rats, Wistar
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Summary:In isolated mitochondria the consequences of oxidative phosphorylation uncoupling are well defined, whereas in intact cells various effects have been described. Uncoupling liver cells with 2,4-dinitrophenol (DNP) in the presence of dihydroxyacetone (DHA) and ethanol results in a marked decrease in mitochondrial transmembrane electrical potential (DeltaPsi), ATP/ADP ratios and gluconeogenesis (as an ATP-utilizing process), whereas the increased oxidation rate is limited and transient. Conversely, when DHA is associated with octanoate or proline, DNP addition results in a very large and sustained increase in oxidation rate, whereas the decreases in DeltaPsi, ATP/ADP ratios and gluconeogenesis are significantly less when compared with DHA and ethanol. Hence significant energy wastage (high oxidation rate) by uncoupling is achieved only with substrates that are directly oxidized in the mitochondrial matrix. Conversely in the presence of substrates that are first oxidized in the cytosol, uncoupling results in a profound decrease in mitochondrial DeltaPsi and ATP synthesis, whereas energy wastage is very limited.
ISSN:0264-6021
1470-8728
DOI:10.1042/0264-6021:3550231