Mitochondrial protonophoric activity induced by a thyromimetic fatty acid analogue.
Calcium-dependent uncoupling of liver mitochondrial oxidative phosphorylation by a non-metabolizable long chain fatty acyl analogue was compared with uncoupling induced by in vivo thyroid hormone treatment. beta,beta'-Methyl-substituted hexadecane alpha, omega-dioic acid (Medica 16) is reported here to induce a saturable 20-30% decrease in liver mitochondrial DeltaPsi, DeltapH and protonmotive force which proceeds in the presence of added Ca(2+) to cyclosporin A-sensitive mitochondrial permeabilization. Ca(2+)-dependent uncoupling by Medica 16 was accompanied by atractylate-enhanced, bongkrekic-inhibited activation of mitochondrial Ca(2+) efflux. The direct mitochondrial effect exerted in vitro by Medica 16 is similar to that induced by in vivo thyroid hormone treatment. Hence, the thyromimetic protonophoric activity of Medica 16 and the uncoupling activity of TH converge onto components of the mitochondrial permeabilization transition pore.
Hermesh
O
O
Department of Human Nutrition and Metabolism, Faculty of Medicine, Hebrew University Medical School, Jerusalem, Israel.
Kalderon
B
B
Berman
B
B
Bar-Tana
J
J
D000818:Animals; D006980:Hyperthyroidism / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007037:Hypothyroidism / Q000378:metabolism; D007473:Ion Channels; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008713:Methimazole; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D010169:Palmitic Acids / Q000494:pharmacology*; D018892:Proton-Motive Force; D051381:Rats; D014284:Triiodothyronine; D014475:Uncoupling Agents
D000960:Hypolipidemic Agents; D007473:Ion Channels; D008565:Membrane Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D010169:Palmitic Acids; D014475:Uncoupling Agents; D014284:Triiodothyronine; D008713:Methimazole; C056166:MEDICA 16