Adenine nucleotide translocator promotes oxidative phosphorylation and mild uncoupling in mitochondria after dexamethasone treatment.
The composition of the mitochondrial inner membrane and uncoupling protein [such as adenine nucleotide translocator (ANT)] contents are the main factors involved in the energy-wasting proton leak. This leak is increased by glucocorticoid treatment under nonphosphorylating conditions. The aim of this study was to investigate mechanisms involved in glucocorticoid-induced proton leak and to evaluate the consequences in more physiological conditions (between states 4 and 3). Isolated liver mitochondria, obtained from dexamethasone-treated rats (1.5 mg.kg(-1).day(-1)), were studied by polarography, Western blotting, and high-performance thin-layer chromatography. We confirmed that dexamethasone treatment in rats induces a proton leak in state 4 that is associated with an increased ANT content, although without any change in membrane surface or lipid composition. Between states 4 and 3, dexamethasone stimulates ATP synthesis by increasing both the mitochondrial ANT and F1-F0 ATP synthase content. In conclusion, dexamethasone increases mitochondrial capacity to generate ATP by modifying ANT and ATP synthase. The side effect is an increased leak in nonphosphorylating conditions.
Arvier
Matthieu
M
Institut National de la Santé et de la Recherche Médicale, Laboratoire de Biochimie et de Biologie Moléculaire, Centre Hospitalier Universitaire, Angers, France.
Lagoutte
Laëtitia
L
Johnson
Gyasi
G
Dumas
Jean-François
JF
Sion
Benoit
B
Grizard
Genevieve
G
Malthièry
Yves
Y
Simard
Gilles
G
Ritz
Patrick
P
D033741:Adenine Nucleotide Translocator 1 / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002308:Cardiolipins / Q000378:metabolism; D002950:Citrate (si)-Synthase / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004983:Ethanolamines / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010713:Phosphatidylcholines / Q000378:metabolism; D011048:Polarography; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D033741:Adenine Nucleotide Translocator 1; D002308:Cardiolipins; D004983:Ethanolamines; D005938:Glucocorticoids; D010713:Phosphatidylcholines; C005448:phosphorylethanolamine; D003907:Dexamethasone; D000255:Adenosine Triphosphate; D002950:Citrate (si)-Synthase; C474451:F1F0-ATP synthase; C497342:ATP synthase beta subunit, rat; D025261:Mitochondrial Proton-Translocating ATPases