Divalent cation chelators citrate and EDTA unmask an intrinsic uncoupling pathway in isolated mitochondria |
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| Authors: | Anatoly A Starkov Christos Chinopoulos Natalia N Starkova Csaba Konrad Gergely Kiss Anna Stepanova Vasily N Popov |
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| Institution: | 1.The Feil Family Brain and Mind Research Institute,Weill Cornell Medical College,New York,USA;2.Department of Medical Biochemistry,Semmelweis University,Budapest,Hungary;3.Department of Hematology and Medical Oncology,Icahn School of Medicine at Mount Sinai,New York,USA;4.School of Biological Sciences, Medical Biology Centre,Queens University Belfast,Belfast,UK;5.Voronezh State University,Voronezh,Russia;6.MTA-SE Lendület Neurobiochemistry Research Group,Budapest,Hungary |
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| Abstract: | We demonstrate a suppression of ROS production and uncoupling of mitochondria by exogenous citrate in Mg2+ free medium. Exogenous citrate suppressed H2O2 emission and depolarized mitochondria. The depolarization was paralleled by the stimulation of respiration of mitochondria. The uncoupling action of citrate was independent of the presence of sodium, potassium, or chlorine ions, and it was not mediated by the changes in permeability of the inner mitochondrial membrane to solutes. The citrate transporter was not involved in the citrate effect. Inhibitory analysis data indicated that several well described mitochondria carriers and channels (ATPase, IMAC, ADP/ATP translocase, mPTP, mKATP) were not involved in citrate’s effect. Exogenous MgCl2 strongly inhibited citrate-induced depolarization. The uncoupling effect of citrate was demonstrated in rat brain, mouse brain, mouse liver, and human melanoma cells mitochondria. We interpreted the data as an evidence to the existence of a hitherto undescribed putative inner mitochondrial membrane channel that is regulated by extramitochondrial Mg2+ or other divalent cations. |
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