The lampricide 3-trifluoromethyl-4-nitrophenol (TFM) uncouples mitochondrial oxidative phosphorylation in both sea lamprey (Petromyzon marinus) and TFM-tolerant rainbow trout (Oncorhynchus mykiss)

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• 作者：Oana Birceanu^a ; ^{obircean@uwaterloo.ca} ; Grant B. McClelland^b ; ^{grantm@mcmaster.ca} ; Yuxiang S. Wang^c ; ^{yuxiangw@queensu.ca} ; Jason C.L. Brown^d ; ^{jbrow63@uwo.ca} ; Michael P. Wilkie^a ; ^{mwilkie@wlu.ca}
• 关键词：Mitochondrial transmembrane potential ; Respiratory control ratio ; 2 ; 4-dinitrophenol ; Invasive species ; Integrated pest management ; Pesticide ; State III respiration ; State IV respiration ; Great Lakes
• 刊名：Comparative Biochemistry and Physiology, Part C
• 出版年：2011
• 出版时间：April 2011
• 年：2011
• 卷：153
• 期：3
• 页码：342-349
• 全文大小：528 K

文摘

The toxicity of 3-trifluoromethyl-4-nitrophenol (TFM) appears to be due to a mismatch between ATP supply and demand in lamprey, depleting glycogen stores and starving the nervous system of ATP. The cause of this TFM-induced ATP deficit is unclear. One possibility is that TFM uncouples mitochondrial oxidative phosphorylation, thus impairing ATP production. To test this hypothesis, mitochondria were isolated from the livers of sea lamprey and rainbow trout, and O₂ consumption rates were measured in the presence of TFM or 2,4-dinitrophenol (2,4-DNP), a known uncoupler of oxidative phosphorylation. TFM and 2,4-DNP markedly increased State IV respiration in a dose-dependent fashion, but had no effect on State III respiration, which is consistent with uncoupling of oxidative phosphorylation. To determine how TFM uncoupled oxidative phosphorylation, the mitochondrial transmembrane potential (TMP) was recorded using the mitochondria-specific dye rhodamine 123. Mitochondrial TMP decreased by 22 % in sea lamprey, and by 28 % in trout following treatment with 50 μmol L^− 1 TFM. These findings suggest that TFM acted as a protonophore, dissipating the proton motive force needed to drive ATP synthesis. We conclude that the mode of TFM toxicity in sea lamprey and rainbow trout is via uncoupling of oxidative phosphorylation, leading to impaired ATP production.