Wieckowski M R, Wojtczak L
Nencki Institute of Experimental Biology, Warsaw, Poland.
FEBS Lett. 1998 Feb 27;423(3):339-42. doi: 10.1016/s0014-5793(98)00118-5.
Addition of myristate at low concentration (30-60 nmol/mg protein) to energized rat liver mitochondria resulted in dissipation of the electric membrane potential which, in Ca2+-free media, could be partly reversed by carboxyatractyloside but not by cyclosporin A. In contrast, in mitochondria preloaded with Ca2+ this energy-dissipating effect of fatty acid was partly prevented or reversed by cyclosporin A or ADP. In sucrose media, myristate, but not the protonophore carbonyl cyanide m-chlorophenylhydrazone, induced swelling of Ca2+-loaded mitochondria which was inhibited by cyclosporin A and ADP. We conclude that long-chain fatty acids may induce opening of the mitochondrial permeability transition pore not only because of their protonophoric effect mediated by mitochondrial anion carriers [Skulachev, V.P., FEBS Lett. 294 (1991) 158-162; Wieckowski, M.R. and Wojtczak, L., Biochem. Biophys. Res. Commun. (1997) 232, 414-417] but also by a direct interaction with the pore assembly.
在向有活力的大鼠肝脏线粒体中添加低浓度（30 - 60 nmol/mg蛋白质）的肉豆蔻酸盐后，导致了跨膜电位的耗散，在无Ca2 + 的介质中，这种情况可被羧基苍术苷部分逆转，但不能被环孢菌素A逆转。相反，在预先加载了Ca2 + 的线粒体中，脂肪酸的这种能量耗散效应可被环孢菌素A或ADP部分阻止或逆转。在蔗糖介质中，肉豆蔻酸盐而非质子载体羰基氰化物间氯苯腙可诱导Ca2 + 负载的线粒体肿胀，这种肿胀可被环孢菌素A和ADP抑制。我们得出结论，长链脂肪酸可能诱导线粒体通透性转换孔开放，这不仅是因为它们通过线粒体阴离子载体介导的质子载体效应[Skulachev, V.P., FEBS Lett. 294 (1991) 158 - 162; Wieckowski, M.R. and Wojtczak, L., Biochem. Biophys. Res. Commun. (1997) 232, 414 - 417]，还因为它们与孔组件的直接相互作用。
