Kupsch 2009 FEBS J

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Kupsch K, Hertel S, Kreutzmann P, Wolf G, Wallesch CW, Siemen D, Schönfeld P (2009) Impairment of mitochondrial function by minocycline. FEBS J 276:1729–38.

» PMID: 19243427 ; Open Access

Kupsch K, Hertel S, Kreutzmann P, Wolf G, Wallesch CW, Siemen D, Schoenfeld P (2009) FEBS J

Abstract: There is an ongoing debate on the presence of beneficial effects of minocycline (MC), a tetracycline-like antibiotic, on the preservation of mitochondrial functions under conditions promoting mitochondria-mediated apoptosis. Here, we present a multiparameter study on the effects of MC on isolated rat liver mitochondria (RLM) suspended either in a KCl-based or in a sucrose-based medium. We found that the incubation medium used strongly affects the response of RLM to MC. In KCl-based medium, but not in sucrose-based medium, MC triggered mitochondrial swelling and cytochrome c release. MC-dependent swelling was associated with mitochondrial depolarization and a decrease in state 3 as well as uncoupled respiration. Swelling of RLM in KCl-based medium indicates that MC permeabilizes the inner mitochondrial membrane (IMM) to K+ and Cl). This view is supported by our findings that MC-induced swelling in the KClbased medium was partly suppressed by N,N¢-dicyclohexylcarbodiimide (an inhibitor of IMM-linked K+-transport) and tributyltin (an inhibitor of the inner membrane anion channel) and that swelling was less pronounced when RLM were suspended in choline chloride-based medium. In addition, we observed a rapid MC-induced depletion of endogenous Mg2+ from RLM, an event that is known to activate ion-conducting pathways within the IMM. Moreover, MC abolished the Ca2+ retention capacity of RLM irrespective of the incubation medium used, most likely by triggering permeability transition. In summary, we found that MC at low micromolar concentrations impairs several energy-dependent functions of mitochondria in vitro.

Keywords: Magnesium, Minocycline, Mitochondria, Neuroprotection, Permeability transition

O2k-Network Lab: DE Magdeburg Siemen D, DE Magdeburg Schoenfeld P


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Organism: Rat  Tissue;cell: Liver  Preparation: Isolated mitochondria 



HRR: Oxygraph-2k 


Correction

An Oroboros O2k was used in this publication, whereas the Anton Paar/Oroboros Oxygraph was the first-generation instrument for high-resolution respirometry, which was replaced by the Oxygraph-2k in 2002.