Belosludtsev K N, Belosludtseva N V, Mironova G D
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region, 142290, Russia.
Biochemistry (Mosc). 2005 Jul;70(7):815-21. doi: 10.1007/s10541-005-0189-x.
The mechanism of the palmitate-induced opening of the mitochondrial Ca2+-dependent cyclosporin A (CsA)-insensitive pore was studied, as well as the influence on this process of well-known modulators of the CsA-sensitive Ca2+-dependent pore. Palmitic acid, which can bind Ca2+ with high affinity, induced the cyclosporin A-insensitive swelling of mitochondria, whereas palmitoleic and 2-bromopalmitic acids, which have no such affinity for Ca2+, failed to induce the pore opening. The palmitate-induced Ca2+-dependent swelling of mitochondria was not affected by a well-known inhibitor of the CsA-sensitive pore (ADP) and an activator of this pore (inorganic phosphate, P(i)). However, this swelling was inhibited by physiological concentrations of ATP ([I]50 = 1.3 mM), but 100 microM ATP increased by 30% the rate of mitochondria swelling if Ca2+ had been added earlier. The effects of ATP (inhibition and activation) manifested themselves from different sides of the inner mitochondrial membrane. Mg2+ inhibited the palmitate-induced Ca2+-dependent swelling of mitochondria with [I]50 = 0.8 mM. It is concluded that palmitic acid induces the opening of the CsA-insensitive pore due to its ability for complexing with Ca2+. A possible mechanism of the pore formation and the influence of some modulators on this process are discussed.
研究了棕榈酸诱导的线粒体钙离子依赖性环孢菌素A（CsA）不敏感孔开放的机制，以及CsA敏感的钙离子依赖性孔的知名调节剂对该过程的影响。能与钙离子高亲和力结合的棕榈酸可诱导线粒体对环孢菌素A不敏感的肿胀，而对钙离子无此亲和力的棕榈油酸和2-溴棕榈酸则不能诱导孔开放。棕榈酸诱导的线粒体钙离子依赖性肿胀不受CsA敏感孔的知名抑制剂（ADP）和该孔的激活剂（无机磷酸盐，P(i)）的影响。然而，这种肿胀受到生理浓度ATP（[I]50 = 1.3 mM）的抑制，但如果较早添加钙离子，100 microM ATP可使线粒体肿胀速率提高30%。ATP的作用（抑制和激活）在线粒体内膜的不同侧表现出来。镁离子以[I]50 = 0.8 mM抑制棕榈酸诱导的线粒体钙离子依赖性肿胀。得出的结论是，棕榈酸因其与钙离子络合的能力而诱导CsA不敏感孔的开放。讨论了孔形成的可能机制以及一些调节剂对该过程的影响。
