Difference between revisions of "Kupsch 2009 FEBS J"

Latest revision as of 10:58, 23 January 2019

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

Labels:

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.

Further details: Gnaiger 2012 Abstract Bioblast-Gentle Science

@@ Line 1: / Line 1: @@
 {{Publication
-|title=Kupsch K, Hertel S, Kreutzmann P, Wolf G, Wallesch CW, Siemen D, Schönfeld P (2009) Impairment of mitochondrial function by minocycline. FEBS J. 276: 1729–1738.
+|title=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.
+|info=[http://www.ncbi.nlm.nih.gov/pubmed/19243427 PMID: 19243427] ; [http://dx.doi.org/10.1111/j.1742-4658.2009.06904.x Open Access]
 |authors=Kupsch K, Hertel S, Kreutzmann P, Wolf G, Wallesch CW, Siemen D, Schoenfeld P
 |year=2009
-|journal=FEBS J.
+|journal=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
@@ Line 15: / Line 16: @@
 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
+the inner mitochondrial membrane (IMM) to K<sup>+</sup> 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
+inhibitor of IMM-linked K<sup>+</sup>-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
+we observed a rapid MC-induced depletion of endogenous Mg<sup>2+</sup> from
 RLM, an event that is known to activate ion-conducting pathways within
-the IMM. Moreover, MC abolished the Ca2+ retention capacity of RLM
+the IMM. Moreover, MC abolished the Ca<sup>2+</sup> retention capacity of RLM
-irrespective of the incubation medium used, most likely by triggering permeability
+irrespective of the incubation medium used, most likely by triggering permeability transition. In summary, we found that MC at low micromolar
-transition. In summary, we found that MC at low micromolar
 concentrations impairs several energy-dependent functions of mitochondria
-in vitro.
+''in vitro''.
 |keywords=Magnesium, Minocycline, Mitochondria, Neuroprotection, Permeability transition
+|mipnetlab=DE Magdeburg Siemen D, DE Magdeburg Schoenfeld P
+|discipline=Mitochondrial Physiology
 }}
 {{Labeling
-|discipline=Mitochondrial Physiology
-|injuries=Cancer; Apoptosis; Cytochrome c
 |organism=Rat
-|tissues=Hepatocyte; Liver
+|tissues=Liver
-|preparations=Isolated Mitochondria
+|preparations=Isolated mitochondria
-|topics=Respiration; OXPHOS; ETS Capacity, Coupling; Membrane Potential
 |instruments=Oxygraph-2k
+|discipline=Mitochondrial Physiology
 }}
+== 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.
+* ''Further details'': [[Gnaiger 2012 Abstract Bioblast-Gentle Science]]