Mitochondrial protonophoric activity induced by a thyromimetic fatty acid analogue

Calcium-dependent uncoupling of liver mitochondrial oxidative phosphorylati on 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 heir to induce a saturable 20-30% decrease in liver mitochondrial Delta Psi, Del ta pH and protonmotive force which proceeds in the presence of added Ca2+ t o cyclosporin A-sensitive mitochondrial permeabilization. Ca2+-dependent un coupling by Medica 16 was accompanied by atractylate-enhanced, bongkrekic-i nhibited activation of mitochondrial Ca2+ 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 o f Medica 16 and the uncoupling activity of TH converge onto components of t he mitochondrial permeabilization transition pore, (C) 2000 Elsevier Scienc e B.V, All rights reserved.