Oligomycin A is an inhibitor of ATP synthase, which inhibits the process taking place on mitochondria coupling membrane that depended on ATP and oxidative phosphorylation [1].
Oligomycin A produced a concentration-dependent block of Icrac with similar characteristics, but with lower potency than oligomycin B. Fits of averaged concentration-response data to a logistic function yielded IC50 values and slope factor coefficients (respectively) of 13.5 μM and 0.85 for oligomycin A, and 2.3 μM and 0.82 for oligomycin B. A two-way analysis of variance confirmed a significantly greater inhibition by oligomycin B over the concentration range tested [2].
Oligomycin A treated Wt(widetype) mice have decreased ATP levels in the liver. Concomitantly, these mice showed an enhanced apoptosis in hepatocytes as Tg mice after LPS/GalN administration [3]. Further activation of AMPK was detected in Wt mice after treatment with oligomycin A. Collectively, these data demonstrated that UCP2 expression in hepatocytes could alter mitochondrial parameters leading to activation of AMPK [3].
References:
[1]. Jastroch M, Divakaruni AS, Mookerjee S, et al. Mitochondrial proton and electron leaks. Essays Biochemistry, 2010, 47:53-67.
[2]. Cho, J.H., M. Balasubramanyam, G. Chernaya, J.P. Gardner, A. Aviv, J.P. Reeves, P.G. Dargis, and E.P. Christian. Oligomycin inhibits storeoperated channels by a mechanism independent of its effects on mitochondrial ATP. Biochem. J. 1997.324:971-980.
[3]. Shang Y, Liu Y, Du L, Wang Y, et al. Targeted expression of uncoupling protein 2 to mouse liver increases the susceptibility to lipopolysaccharide/galactosamine-induced acute liver injury. Hepatology 2009, 50: 1204-1216
Oligomycin A 是一种 ATP 合酶抑制剂，可抑制线粒体偶联膜上依赖 ATP 和氧化磷酸化的过程[1]。
Oligomycin A 产生了 Icrac 的浓度依赖性块，具有相似的特性，但效力低于寡霉素 B。平均浓度-响应数据与逻辑函数的拟合产生 IC50 值和斜率系数（分别）为 13.5 μM 和寡霉素 A 为 0.85，寡霉素 B 为 2.3 μM 和 0.82。双向方差分析证实寡霉素 B 在测试的浓度范围内具有显着更强的抑制作用[2]。
寡霉素 A 处理的 Wt（宽型）小鼠肝脏中的 ATP 水平降低。同时，这些小鼠在 LPS/GalN 给药后表现出与 Tg 小鼠一样肝细胞凋亡增强 [3]。在用寡霉素 A 处理后的 Wt 小鼠中检测到 AMPK 的进一步激活。总的来说，这些数据表明肝细胞中 UCP2 的表达可以改变线粒体参数，从而导致 AMPK 激活 [3]。