Hermesh O, Kalderon B, Bar-Tana J
Department of Human Nutrition and Metabolism, Faculty of Medicine, Hebrew University, P. O. Box 12272, Jerusalem 91120, Israel.
J Biol Chem. 1998 Feb 13;273(7):3937-42. doi: 10.1074/jbc.273.7.3937.
Mitochondria uncoupling by fatty acids in vivo is still questionable, being confounded by their dual role as substrates for oxidation and as putative genuine uncouplers of oxidative phosphorylation. To dissociate between substrate and the uncoupling activity of fatty acids in oxidative phosphorylation, the uncoupling effect was studied here using a nonmetabolizable long chain fatty acyl analogue. beta,beta'-Methyl-substituted hexadecane alpha,omega-dioic acid (MEDICA 16) is reported here to induce in freshly isolated liver cells a saturable oligomycin-insensitive decrease in mitochondrial proton motive force with a concomitant increase in cellular respiration. Similarly, MEDICA 16 induced a saturable decrease in membrane potential, proton gradient, and proton motive force in isolated liver and heart mitochondria accompanied by an increase in mitochondrial respiration. Uncoupling by MEDICA 16 in isolated mitochondria was partially suppressed by added atractyloside. Hence, fatty acids may act as genuine uncouplers of cellular oxidative phosphorylation by interacting with specific mitochondrial proteins, including the adenine nucleotide translocase.
脂肪酸在体内使线粒体解偶联的现象仍存在疑问，这是因为脂肪酸作为氧化底物和氧化磷酸化潜在的真正解偶联剂的双重作用而变得复杂。为了区分脂肪酸在氧化磷酸化中的底物作用和解偶联活性，本文使用一种不可代谢的长链脂肪酰类似物研究了解偶联效应。本文报道，β,β'-甲基取代的十六烷二酸（MEDICA 16）可在新鲜分离的肝细胞中诱导线粒体质子动力势出现饱和的、对寡霉素不敏感的降低，并伴随细胞呼吸增加。同样，MEDICA 16可使分离的肝脏和心脏线粒体的膜电位、质子梯度和质子动力势出现饱和降低，并伴随线粒体呼吸增加。在分离的线粒体中，MEDICA 16引起的解偶联作用被加入的苍术苷部分抑制。因此，脂肪酸可能通过与特定的线粒体蛋白（包括腺嘌呤核苷酸转位酶）相互作用，作为细胞氧化磷酸化的真正解偶联剂。
