Divalent cation chelators citrate and EDTA unmask an intrinsic uncoupling pathway in isolated mitochondria.

TitleDivalent cation chelators citrate and EDTA unmask an intrinsic uncoupling pathway in isolated mitochondria.
Publication TypeJournal Article
Year of Publication2017
AuthorsStarkov AA, Chinopoulos C, Starkova NN, Konrad C, Kiss G, Stepanova A, Popov VN
JournalJ Bioenerg Biomembr
Date Published2017 Feb
KeywordsAnimals, Biological Transport, Brain, Cations, Divalent, Citric Acid, Edetic Acid, Humans, Hydrogen Peroxide, Ion Channels, Magnesium Chloride, Melanoma, Mice, Mitochondria, Mitochondrial Membranes, Rats, Reactive Oxygen Species

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.

Alternate JournalJ. Bioenerg. Biomembr.
PubMed ID26971498
PubMed Central IDPMC5023464
Grant ListP01 AG014930 / AG / NIA NIH HHS / United States