PittsburghV1, PubMed, Curation, bibRecord, 000A41

The mitochondrial complex V-associated large-conductance inner membrane current is regulated by cyclosporine and dexpramipexole.

Identifieur interne : 000A41 ( PubMed/Curation ); précédent : 000A40; suivant : 000A42

The mitochondrial complex V-associated large-conductance inner membrane current is regulated by cyclosporine and dexpramipexole.

Auteurs : Kambiz N. Alavian ; Steven I. Dworetzky ; Laura Bonanni ; Ping Zhang ; Silvio Sacchetti ; Hongmei Li ; Armando P. Signore ; Peter J S. Smith ; Valentin K. Gribkoff ; Elizabeth A. Jonas [États-Unis]

Source :

Molecular pharmacology [ 1521-0111 ] ; 2015.

RBID : pubmed:25332381

Descripteurs français

KwdFr :
- Adénosine triphosphate (métabolisme), Adénosine triphosphate (pharmacologie), Benzothiazoles (pharmacologie), Ciclosporine (pharmacologie), Encéphale (cytologie), Encéphale (enzymologie), Humains, Membranes mitochondriales (), Proton-Translocating ATPases (métabolisme), Protéines de transport de la membrane mitochondriale (métabolisme).
MESH :
- cytologie : Encéphale.
- enzymologie : Encéphale.
- métabolisme : Adénosine triphosphate, Proton-Translocating ATPases, Protéines de transport de la membrane mitochondriale.
- pharmacologie : Adénosine triphosphate, Benzothiazoles, Ciclosporine.
- Humains, Membranes mitochondriales.

English descriptors

KwdEn :
- Adenosine Triphosphate (metabolism), Adenosine Triphosphate (pharmacology), Benzothiazoles (pharmacology), Brain (cytology), Brain (enzymology), Cyclosporine (pharmacology), Humans, Mitochondrial Membrane Transport Proteins (metabolism), Mitochondrial Membranes (drug effects), Proton-Translocating ATPases (metabolism).
MESH :
- chemical , metabolism : Adenosine Triphosphate, Mitochondrial Membrane Transport Proteins, Proton-Translocating ATPases.
- chemical , pharmacology : Adenosine Triphosphate, Benzothiazoles, Cyclosporine.
- cytology : Brain.
- drug effects : Mitochondrial Membranes.
- enzymology : Brain.
- Humans.

Abstract

Inefficiency of oxidative phosphorylation can result from futile leak conductance through the inner mitochondrial membrane. Stress or injury may exacerbate this leak conductance, putting cells, and particularly neurons, at risk of dysfunction and even death when energy demand exceeds cellular energy production. Using a novel method, we have recently described an ion conductance consistent with mitochondrial permeability transition pore (mPTP) within the c-subunit of the ATP synthase. Excitotoxicity, reactive oxygen species-producing stimuli, or elevated mitochondrial matrix calcium opens the channel, which is inhibited by cyclosporine A and ATP/ADP. Here we show that ATP and the neuroprotective drug dexpramipexole (DEX) inhibited an ion conductance consistent with this c-subunit channel (mPTP) in brain-derived submitochondrial vesicles (SMVs) enriched for F1FO ATP synthase (complex V). Treatment of SMVs with urea denatured extramembrane components of complex V, eliminated DEX- but not ATP-mediated current inhibition, and reduced binding of [(14)C]DEX. Direct effects of DEX on the synthesis and hydrolysis of ATP by complex V suggest that interaction of the compound with its target results in functional conformational changes in the enzyme complex. [(14)C]DEX bound specifically to purified recombinant b and oligomycin sensitivity-conferring protein subunits of the mitochondrial F1FO ATP synthase. Previous data indicate that DEX increased the efficiency of energy production in cells, including neurons. Taken together, these studies suggest that modulation of a complex V-associated inner mitochondrial membrane current is metabolically important and may represent an avenue for the development of new therapeutics for neurodegenerative disorders.

DOI: 10.1124/mol.114.095661
PubMed: 25332381

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Kambiz N. Alavian

<affiliation><nlm:affiliation>Department of Internal Medicine (K.N.A., P.Z., S.S., H.L., E.A.J.) and Department of Neurobiology (E.A.J.), Yale University School of Medicine, New Haven, Connecticut; Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom (K.N.A.); Department of Neuroscience, Imaging and Clinical Sciences, University G.d'Annunzio of Chieti-Pescara, Chieti-Pescara, Italy (L.B.); Knopp Biosciences LLC, Pittsburgh, Pennsylvania (S.I.D., A.P.S., V.K.G.); and Biocurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts (P.J.S.S.).</nlm:affiliation>
<wicri:noCountry code="subField">Massachusetts (P.J.S.S.).</wicri:noCountry>
</affiliation>

Steven I. Dworetzky

<affiliation><nlm:affiliation>Department of Internal Medicine (K.N.A., P.Z., S.S., H.L., E.A.J.) and Department of Neurobiology (E.A.J.), Yale University School of Medicine, New Haven, Connecticut; Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom (K.N.A.); Department of Neuroscience, Imaging and Clinical Sciences, University G.d'Annunzio of Chieti-Pescara, Chieti-Pescara, Italy (L.B.); Knopp Biosciences LLC, Pittsburgh, Pennsylvania (S.I.D., A.P.S., V.K.G.); and Biocurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts (P.J.S.S.).</nlm:affiliation>
<wicri:noCountry code="subField">Massachusetts (P.J.S.S.).</wicri:noCountry>
</affiliation>

Laura Bonanni

<affiliation><nlm:affiliation>Department of Internal Medicine (K.N.A., P.Z., S.S., H.L., E.A.J.) and Department of Neurobiology (E.A.J.), Yale University School of Medicine, New Haven, Connecticut; Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom (K.N.A.); Department of Neuroscience, Imaging and Clinical Sciences, University G.d'Annunzio of Chieti-Pescara, Chieti-Pescara, Italy (L.B.); Knopp Biosciences LLC, Pittsburgh, Pennsylvania (S.I.D., A.P.S., V.K.G.); and Biocurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts (P.J.S.S.).</nlm:affiliation>
<wicri:noCountry code="subField">Massachusetts (P.J.S.S.).</wicri:noCountry>
</affiliation>

Ping Zhang

<affiliation><nlm:affiliation>Department of Internal Medicine (K.N.A., P.Z., S.S., H.L., E.A.J.) and Department of Neurobiology (E.A.J.), Yale University School of Medicine, New Haven, Connecticut; Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom (K.N.A.); Department of Neuroscience, Imaging and Clinical Sciences, University G.d'Annunzio of Chieti-Pescara, Chieti-Pescara, Italy (L.B.); Knopp Biosciences LLC, Pittsburgh, Pennsylvania (S.I.D., A.P.S., V.K.G.); and Biocurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts (P.J.S.S.).</nlm:affiliation>
<wicri:noCountry code="subField">Massachusetts (P.J.S.S.).</wicri:noCountry>
</affiliation>

Silvio Sacchetti

<affiliation><nlm:affiliation>Department of Internal Medicine (K.N.A., P.Z., S.S., H.L., E.A.J.) and Department of Neurobiology (E.A.J.), Yale University School of Medicine, New Haven, Connecticut; Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom (K.N.A.); Department of Neuroscience, Imaging and Clinical Sciences, University G.d'Annunzio of Chieti-Pescara, Chieti-Pescara, Italy (L.B.); Knopp Biosciences LLC, Pittsburgh, Pennsylvania (S.I.D., A.P.S., V.K.G.); and Biocurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts (P.J.S.S.).</nlm:affiliation>
<wicri:noCountry code="subField">Massachusetts (P.J.S.S.).</wicri:noCountry>
</affiliation>

Hongmei Li

<affiliation><nlm:affiliation>Department of Internal Medicine (K.N.A., P.Z., S.S., H.L., E.A.J.) and Department of Neurobiology (E.A.J.), Yale University School of Medicine, New Haven, Connecticut; Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom (K.N.A.); Department of Neuroscience, Imaging and Clinical Sciences, University G.d'Annunzio of Chieti-Pescara, Chieti-Pescara, Italy (L.B.); Knopp Biosciences LLC, Pittsburgh, Pennsylvania (S.I.D., A.P.S., V.K.G.); and Biocurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts (P.J.S.S.).</nlm:affiliation>
<wicri:noCountry code="subField">Massachusetts (P.J.S.S.).</wicri:noCountry>
</affiliation>

Armando P. Signore

<affiliation><nlm:affiliation>Department of Internal Medicine (K.N.A., P.Z., S.S., H.L., E.A.J.) and Department of Neurobiology (E.A.J.), Yale University School of Medicine, New Haven, Connecticut; Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom (K.N.A.); Department of Neuroscience, Imaging and Clinical Sciences, University G.d'Annunzio of Chieti-Pescara, Chieti-Pescara, Italy (L.B.); Knopp Biosciences LLC, Pittsburgh, Pennsylvania (S.I.D., A.P.S., V.K.G.); and Biocurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts (P.J.S.S.).</nlm:affiliation>
<wicri:noCountry code="subField">Massachusetts (P.J.S.S.).</wicri:noCountry>
</affiliation>

Peter J S. Smith

<affiliation><nlm:affiliation>Department of Internal Medicine (K.N.A., P.Z., S.S., H.L., E.A.J.) and Department of Neurobiology (E.A.J.), Yale University School of Medicine, New Haven, Connecticut; Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom (K.N.A.); Department of Neuroscience, Imaging and Clinical Sciences, University G.d'Annunzio of Chieti-Pescara, Chieti-Pescara, Italy (L.B.); Knopp Biosciences LLC, Pittsburgh, Pennsylvania (S.I.D., A.P.S., V.K.G.); and Biocurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts (P.J.S.S.).</nlm:affiliation>
<wicri:noCountry code="subField">Massachusetts (P.J.S.S.).</wicri:noCountry>
</affiliation>

Valentin K. Gribkoff

<affiliation><nlm:affiliation>Department of Internal Medicine (K.N.A., P.Z., S.S., H.L., E.A.J.) and Department of Neurobiology (E.A.J.), Yale University School of Medicine, New Haven, Connecticut; Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom (K.N.A.); Department of Neuroscience, Imaging and Clinical Sciences, University G.d'Annunzio of Chieti-Pescara, Chieti-Pescara, Italy (L.B.); Knopp Biosciences LLC, Pittsburgh, Pennsylvania (S.I.D., A.P.S., V.K.G.); and Biocurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts (P.J.S.S.).</nlm:affiliation>
<wicri:noCountry code="subField">Massachusetts (P.J.S.S.).</wicri:noCountry>
</affiliation>

Le document en format XML

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<author><name sortKey="Zhang, Ping" sort="Zhang, Ping" uniqKey="Zhang P" first="Ping" last="Zhang">Ping Zhang</name>
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<author><name sortKey="Li, Hongmei" sort="Li, Hongmei" uniqKey="Li H" first="Hongmei" last="Li">Hongmei Li</name>
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<author><name sortKey="Signore, Armando P" sort="Signore, Armando P" uniqKey="Signore A" first="Armando P" last="Signore">Armando P. Signore</name>
<affiliation><nlm:affiliation>Department of Internal Medicine (K.N.A., P.Z., S.S., H.L., E.A.J.) and Department of Neurobiology (E.A.J.), Yale University School of Medicine, New Haven, Connecticut; Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom (K.N.A.); Department of Neuroscience, Imaging and Clinical Sciences, University G.d'Annunzio of Chieti-Pescara, Chieti-Pescara, Italy (L.B.); Knopp Biosciences LLC, Pittsburgh, Pennsylvania (S.I.D., A.P.S., V.K.G.); and Biocurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts (P.J.S.S.).</nlm:affiliation>
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<author><name sortKey="Smith, Peter J S" sort="Smith, Peter J S" uniqKey="Smith P" first="Peter J S" last="Smith">Peter J S. Smith</name>
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<wicri:noCountry code="subField">Massachusetts (P.J.S.S.).</wicri:noCountry>
</affiliation>
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<wicri:noCountry code="subField">Massachusetts (P.J.S.S.).</wicri:noCountry>
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<author><name sortKey="Jonas, Elizabeth A" sort="Jonas, Elizabeth A" uniqKey="Jonas E" first="Elizabeth A" last="Jonas">Elizabeth A. Jonas</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">The mitochondrial complex V-associated large-conductance inner membrane current is regulated by cyclosporine and dexpramipexole.</title>
<author><name sortKey="Alavian, Kambiz N" sort="Alavian, Kambiz N" uniqKey="Alavian K" first="Kambiz N" last="Alavian">Kambiz N. Alavian</name>
<affiliation><nlm:affiliation>Department of Internal Medicine (K.N.A., P.Z., S.S., H.L., E.A.J.) and Department of Neurobiology (E.A.J.), Yale University School of Medicine, New Haven, Connecticut; Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom (K.N.A.); Department of Neuroscience, Imaging and Clinical Sciences, University G.d'Annunzio of Chieti-Pescara, Chieti-Pescara, Italy (L.B.); Knopp Biosciences LLC, Pittsburgh, Pennsylvania (S.I.D., A.P.S., V.K.G.); and Biocurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts (P.J.S.S.).</nlm:affiliation>
<wicri:noCountry code="subField">Massachusetts (P.J.S.S.).</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Dworetzky, Steven I" sort="Dworetzky, Steven I" uniqKey="Dworetzky S" first="Steven I" last="Dworetzky">Steven I. Dworetzky</name>
<affiliation><nlm:affiliation>Department of Internal Medicine (K.N.A., P.Z., S.S., H.L., E.A.J.) and Department of Neurobiology (E.A.J.), Yale University School of Medicine, New Haven, Connecticut; Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom (K.N.A.); Department of Neuroscience, Imaging and Clinical Sciences, University G.d'Annunzio of Chieti-Pescara, Chieti-Pescara, Italy (L.B.); Knopp Biosciences LLC, Pittsburgh, Pennsylvania (S.I.D., A.P.S., V.K.G.); and Biocurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts (P.J.S.S.).</nlm:affiliation>
<wicri:noCountry code="subField">Massachusetts (P.J.S.S.).</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Bonanni, Laura" sort="Bonanni, Laura" uniqKey="Bonanni L" first="Laura" last="Bonanni">Laura Bonanni</name>
<affiliation><nlm:affiliation>Department of Internal Medicine (K.N.A., P.Z., S.S., H.L., E.A.J.) and Department of Neurobiology (E.A.J.), Yale University School of Medicine, New Haven, Connecticut; Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom (K.N.A.); Department of Neuroscience, Imaging and Clinical Sciences, University G.d'Annunzio of Chieti-Pescara, Chieti-Pescara, Italy (L.B.); Knopp Biosciences LLC, Pittsburgh, Pennsylvania (S.I.D., A.P.S., V.K.G.); and Biocurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts (P.J.S.S.).</nlm:affiliation>
<wicri:noCountry code="subField">Massachusetts (P.J.S.S.).</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Zhang, Ping" sort="Zhang, Ping" uniqKey="Zhang P" first="Ping" last="Zhang">Ping Zhang</name>
<affiliation><nlm:affiliation>Department of Internal Medicine (K.N.A., P.Z., S.S., H.L., E.A.J.) and Department of Neurobiology (E.A.J.), Yale University School of Medicine, New Haven, Connecticut; Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom (K.N.A.); Department of Neuroscience, Imaging and Clinical Sciences, University G.d'Annunzio of Chieti-Pescara, Chieti-Pescara, Italy (L.B.); Knopp Biosciences LLC, Pittsburgh, Pennsylvania (S.I.D., A.P.S., V.K.G.); and Biocurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts (P.J.S.S.).</nlm:affiliation>
<wicri:noCountry code="subField">Massachusetts (P.J.S.S.).</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Sacchetti, Silvio" sort="Sacchetti, Silvio" uniqKey="Sacchetti S" first="Silvio" last="Sacchetti">Silvio Sacchetti</name>
<affiliation><nlm:affiliation>Department of Internal Medicine (K.N.A., P.Z., S.S., H.L., E.A.J.) and Department of Neurobiology (E.A.J.), Yale University School of Medicine, New Haven, Connecticut; Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom (K.N.A.); Department of Neuroscience, Imaging and Clinical Sciences, University G.d'Annunzio of Chieti-Pescara, Chieti-Pescara, Italy (L.B.); Knopp Biosciences LLC, Pittsburgh, Pennsylvania (S.I.D., A.P.S., V.K.G.); and Biocurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts (P.J.S.S.).</nlm:affiliation>
<wicri:noCountry code="subField">Massachusetts (P.J.S.S.).</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Li, Hongmei" sort="Li, Hongmei" uniqKey="Li H" first="Hongmei" last="Li">Hongmei Li</name>
<affiliation><nlm:affiliation>Department of Internal Medicine (K.N.A., P.Z., S.S., H.L., E.A.J.) and Department of Neurobiology (E.A.J.), Yale University School of Medicine, New Haven, Connecticut; Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom (K.N.A.); Department of Neuroscience, Imaging and Clinical Sciences, University G.d'Annunzio of Chieti-Pescara, Chieti-Pescara, Italy (L.B.); Knopp Biosciences LLC, Pittsburgh, Pennsylvania (S.I.D., A.P.S., V.K.G.); and Biocurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts (P.J.S.S.).</nlm:affiliation>
<wicri:noCountry code="subField">Massachusetts (P.J.S.S.).</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Signore, Armando P" sort="Signore, Armando P" uniqKey="Signore A" first="Armando P" last="Signore">Armando P. Signore</name>
<affiliation><nlm:affiliation>Department of Internal Medicine (K.N.A., P.Z., S.S., H.L., E.A.J.) and Department of Neurobiology (E.A.J.), Yale University School of Medicine, New Haven, Connecticut; Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom (K.N.A.); Department of Neuroscience, Imaging and Clinical Sciences, University G.d'Annunzio of Chieti-Pescara, Chieti-Pescara, Italy (L.B.); Knopp Biosciences LLC, Pittsburgh, Pennsylvania (S.I.D., A.P.S., V.K.G.); and Biocurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts (P.J.S.S.).</nlm:affiliation>
<wicri:noCountry code="subField">Massachusetts (P.J.S.S.).</wicri:noCountry>
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<author><name sortKey="Smith, Peter J S" sort="Smith, Peter J S" uniqKey="Smith P" first="Peter J S" last="Smith">Peter J S. Smith</name>
<affiliation><nlm:affiliation>Department of Internal Medicine (K.N.A., P.Z., S.S., H.L., E.A.J.) and Department of Neurobiology (E.A.J.), Yale University School of Medicine, New Haven, Connecticut; Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom (K.N.A.); Department of Neuroscience, Imaging and Clinical Sciences, University G.d'Annunzio of Chieti-Pescara, Chieti-Pescara, Italy (L.B.); Knopp Biosciences LLC, Pittsburgh, Pennsylvania (S.I.D., A.P.S., V.K.G.); and Biocurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts (P.J.S.S.).</nlm:affiliation>
<wicri:noCountry code="subField">Massachusetts (P.J.S.S.).</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Gribkoff, Valentin K" sort="Gribkoff, Valentin K" uniqKey="Gribkoff V" first="Valentin K" last="Gribkoff">Valentin K. Gribkoff</name>
<affiliation><nlm:affiliation>Department of Internal Medicine (K.N.A., P.Z., S.S., H.L., E.A.J.) and Department of Neurobiology (E.A.J.), Yale University School of Medicine, New Haven, Connecticut; Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom (K.N.A.); Department of Neuroscience, Imaging and Clinical Sciences, University G.d'Annunzio of Chieti-Pescara, Chieti-Pescara, Italy (L.B.); Knopp Biosciences LLC, Pittsburgh, Pennsylvania (S.I.D., A.P.S., V.K.G.); and Biocurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts (P.J.S.S.).</nlm:affiliation>
<wicri:noCountry code="subField">Massachusetts (P.J.S.S.).</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Jonas, Elizabeth A" sort="Jonas, Elizabeth A" uniqKey="Jonas E" first="Elizabeth A" last="Jonas">Elizabeth A. Jonas</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Internal Medicine (K.N.A., P.Z., S.S., H.L., E.A.J.) and Department of Neurobiology (E.A.J.), Yale University School of Medicine, New Haven, Connecticut; Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom (K.N.A.); Department of Neuroscience, Imaging and Clinical Sciences, University G.d'Annunzio of Chieti-Pescara, Chieti-Pescara, Italy (L.B.); Knopp Biosciences LLC, Pittsburgh, Pennsylvania (S.I.D., A.P.S., V.K.G.); and Biocurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts (P.J.S.S.) Elizabeth.jonas@yale.edu.</nlm:affiliation>
<country wicri:rule="url">États-Unis</country>
</affiliation>
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<series><title level="j">Molecular pharmacology</title>
<idno type="eISSN">1521-0111</idno>
<imprint><date when="2015" type="published">2015</date>
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<term>Adenosine Triphosphate (pharmacology)</term>
<term>Benzothiazoles (pharmacology)</term>
<term>Brain (cytology)</term>
<term>Brain (enzymology)</term>
<term>Cyclosporine (pharmacology)</term>
<term>Humans</term>
<term>Mitochondrial Membrane Transport Proteins (metabolism)</term>
<term>Mitochondrial Membranes (drug effects)</term>
<term>Proton-Translocating ATPases (metabolism)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adénosine triphosphate (métabolisme)</term>
<term>Adénosine triphosphate (pharmacologie)</term>
<term>Benzothiazoles (pharmacologie)</term>
<term>Ciclosporine (pharmacologie)</term>
<term>Encéphale (cytologie)</term>
<term>Encéphale (enzymologie)</term>
<term>Humains</term>
<term>Membranes mitochondriales ()</term>
<term>Proton-Translocating ATPases (métabolisme)</term>
<term>Protéines de transport de la membrane mitochondriale (métabolisme)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Adenosine Triphosphate</term>
<term>Mitochondrial Membrane Transport Proteins</term>
<term>Proton-Translocating ATPases</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Adenosine Triphosphate</term>
<term>Benzothiazoles</term>
<term>Cyclosporine</term>
</keywords>
<keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Encéphale</term>
</keywords>
<keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Brain</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Mitochondrial Membranes</term>
</keywords>
<keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Encéphale</term>
</keywords>
<keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Brain</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Adénosine triphosphate</term>
<term>Proton-Translocating ATPases</term>
<term>Protéines de transport de la membrane mitochondriale</term>
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<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Adénosine triphosphate</term>
<term>Benzothiazoles</term>
<term>Ciclosporine</term>
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<keywords scheme="MESH" xml:lang="en"><term>Humans</term>
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<front><div type="abstract" xml:lang="en">Inefficiency of oxidative phosphorylation can result from futile leak conductance through the inner mitochondrial membrane. Stress or injury may exacerbate this leak conductance, putting cells, and particularly neurons, at risk of dysfunction and even death when energy demand exceeds cellular energy production. Using a novel method, we have recently described an ion conductance consistent with mitochondrial permeability transition pore (mPTP) within the c-subunit of the ATP synthase. Excitotoxicity, reactive oxygen species-producing stimuli, or elevated mitochondrial matrix calcium opens the channel, which is inhibited by cyclosporine A and ATP/ADP. Here we show that ATP and the neuroprotective drug dexpramipexole (DEX) inhibited an ion conductance consistent with this c-subunit channel (mPTP) in brain-derived submitochondrial vesicles (SMVs) enriched for F1FO ATP synthase (complex V). Treatment of SMVs with urea denatured extramembrane components of complex V, eliminated DEX- but not ATP-mediated current inhibition, and reduced binding of [(14)C]DEX. Direct effects of DEX on the synthesis and hydrolysis of ATP by complex V suggest that interaction of the compound with its target results in functional conformational changes in the enzyme complex. [(14)C]DEX bound specifically to purified recombinant b and oligomycin sensitivity-conferring protein subunits of the mitochondrial F1FO ATP synthase. Previous data indicate that DEX increased the efficiency of energy production in cells, including neurons. Taken together, these studies suggest that modulation of a complex V-associated inner mitochondrial membrane current is metabolically important and may represent an avenue for the development of new therapeutics for neurodegenerative disorders.</div>
</front>
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<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">25332381</PMID>
<DateCreated><Year>2014</Year>
<Month>11</Month>
<Day>21</Day>
</DateCreated>
<DateCompleted><Year>2015</Year>
<Month>02</Month>
<Day>27</Day>
</DateCompleted>
<DateRevised><Year>2017</Year>
<Month>02</Month>
<Day>20</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1521-0111</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>87</Volume>
<Issue>1</Issue>
<PubDate><Year>2015</Year>
<Month>Jan</Month>
</PubDate>
</JournalIssue>
<Title>Molecular pharmacology</Title>
<ISOAbbreviation>Mol. Pharmacol.</ISOAbbreviation>
</Journal>
<ArticleTitle>The mitochondrial complex V-associated large-conductance inner membrane current is regulated by cyclosporine and dexpramipexole.</ArticleTitle>
<Pagination><MedlinePgn>1-8</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1124/mol.114.095661</ELocationID>
<Abstract><AbstractText>Inefficiency of oxidative phosphorylation can result from futile leak conductance through the inner mitochondrial membrane. Stress or injury may exacerbate this leak conductance, putting cells, and particularly neurons, at risk of dysfunction and even death when energy demand exceeds cellular energy production. Using a novel method, we have recently described an ion conductance consistent with mitochondrial permeability transition pore (mPTP) within the c-subunit of the ATP synthase. Excitotoxicity, reactive oxygen species-producing stimuli, or elevated mitochondrial matrix calcium opens the channel, which is inhibited by cyclosporine A and ATP/ADP. Here we show that ATP and the neuroprotective drug dexpramipexole (DEX) inhibited an ion conductance consistent with this c-subunit channel (mPTP) in brain-derived submitochondrial vesicles (SMVs) enriched for F1FO ATP synthase (complex V). Treatment of SMVs with urea denatured extramembrane components of complex V, eliminated DEX- but not ATP-mediated current inhibition, and reduced binding of [(14)C]DEX. Direct effects of DEX on the synthesis and hydrolysis of ATP by complex V suggest that interaction of the compound with its target results in functional conformational changes in the enzyme complex. [(14)C]DEX bound specifically to purified recombinant b and oligomycin sensitivity-conferring protein subunits of the mitochondrial F1FO ATP synthase. Previous data indicate that DEX increased the efficiency of energy production in cells, including neurons. Taken together, these studies suggest that modulation of a complex V-associated inner mitochondrial membrane current is metabolically important and may represent an avenue for the development of new therapeutics for neurodegenerative disorders.</AbstractText>
<CopyrightInformation>Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Alavian</LastName>
<ForeName>Kambiz N</ForeName>
<Initials>KN</Initials>
<AffiliationInfo><Affiliation>Department of Internal Medicine (K.N.A., P.Z., S.S., H.L., E.A.J.) and Department of Neurobiology (E.A.J.), Yale University School of Medicine, New Haven, Connecticut; Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom (K.N.A.); Department of Neuroscience, Imaging and Clinical Sciences, University G.d'Annunzio of Chieti-Pescara, Chieti-Pescara, Italy (L.B.); Knopp Biosciences LLC, Pittsburgh, Pennsylvania (S.I.D., A.P.S., V.K.G.); and Biocurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts (P.J.S.S.).</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Dworetzky</LastName>
<ForeName>Steven I</ForeName>
<Initials>SI</Initials>
<AffiliationInfo><Affiliation>Department of Internal Medicine (K.N.A., P.Z., S.S., H.L., E.A.J.) and Department of Neurobiology (E.A.J.), Yale University School of Medicine, New Haven, Connecticut; Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom (K.N.A.); Department of Neuroscience, Imaging and Clinical Sciences, University G.d'Annunzio of Chieti-Pescara, Chieti-Pescara, Italy (L.B.); Knopp Biosciences LLC, Pittsburgh, Pennsylvania (S.I.D., A.P.S., V.K.G.); and Biocurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts (P.J.S.S.).</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bonanni</LastName>
<ForeName>Laura</ForeName>
<Initials>L</Initials>
<AffiliationInfo><Affiliation>Department of Internal Medicine (K.N.A., P.Z., S.S., H.L., E.A.J.) and Department of Neurobiology (E.A.J.), Yale University School of Medicine, New Haven, Connecticut; Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom (K.N.A.); Department of Neuroscience, Imaging and Clinical Sciences, University G.d'Annunzio of Chieti-Pescara, Chieti-Pescara, Italy (L.B.); Knopp Biosciences LLC, Pittsburgh, Pennsylvania (S.I.D., A.P.S., V.K.G.); and Biocurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts (P.J.S.S.).</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zhang</LastName>
<ForeName>Ping</ForeName>
<Initials>P</Initials>
<AffiliationInfo><Affiliation>Department of Internal Medicine (K.N.A., P.Z., S.S., H.L., E.A.J.) and Department of Neurobiology (E.A.J.), Yale University School of Medicine, New Haven, Connecticut; Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom (K.N.A.); Department of Neuroscience, Imaging and Clinical Sciences, University G.d'Annunzio of Chieti-Pescara, Chieti-Pescara, Italy (L.B.); Knopp Biosciences LLC, Pittsburgh, Pennsylvania (S.I.D., A.P.S., V.K.G.); and Biocurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts (P.J.S.S.).</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Sacchetti</LastName>
<ForeName>Silvio</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Department of Internal Medicine (K.N.A., P.Z., S.S., H.L., E.A.J.) and Department of Neurobiology (E.A.J.), Yale University School of Medicine, New Haven, Connecticut; Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom (K.N.A.); Department of Neuroscience, Imaging and Clinical Sciences, University G.d'Annunzio of Chieti-Pescara, Chieti-Pescara, Italy (L.B.); Knopp Biosciences LLC, Pittsburgh, Pennsylvania (S.I.D., A.P.S., V.K.G.); and Biocurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts (P.J.S.S.).</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Li</LastName>
<ForeName>Hongmei</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>Department of Internal Medicine (K.N.A., P.Z., S.S., H.L., E.A.J.) and Department of Neurobiology (E.A.J.), Yale University School of Medicine, New Haven, Connecticut; Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom (K.N.A.); Department of Neuroscience, Imaging and Clinical Sciences, University G.d'Annunzio of Chieti-Pescara, Chieti-Pescara, Italy (L.B.); Knopp Biosciences LLC, Pittsburgh, Pennsylvania (S.I.D., A.P.S., V.K.G.); and Biocurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts (P.J.S.S.).</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Signore</LastName>
<ForeName>Armando P</ForeName>
<Initials>AP</Initials>
<AffiliationInfo><Affiliation>Department of Internal Medicine (K.N.A., P.Z., S.S., H.L., E.A.J.) and Department of Neurobiology (E.A.J.), Yale University School of Medicine, New Haven, Connecticut; Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom (K.N.A.); Department of Neuroscience, Imaging and Clinical Sciences, University G.d'Annunzio of Chieti-Pescara, Chieti-Pescara, Italy (L.B.); Knopp Biosciences LLC, Pittsburgh, Pennsylvania (S.I.D., A.P.S., V.K.G.); and Biocurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts (P.J.S.S.).</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Smith</LastName>
<ForeName>Peter J S</ForeName>
<Initials>PJ</Initials>
<AffiliationInfo><Affiliation>Department of Internal Medicine (K.N.A., P.Z., S.S., H.L., E.A.J.) and Department of Neurobiology (E.A.J.), Yale University School of Medicine, New Haven, Connecticut; Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom (K.N.A.); Department of Neuroscience, Imaging and Clinical Sciences, University G.d'Annunzio of Chieti-Pescara, Chieti-Pescara, Italy (L.B.); Knopp Biosciences LLC, Pittsburgh, Pennsylvania (S.I.D., A.P.S., V.K.G.); and Biocurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts (P.J.S.S.).</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Gribkoff</LastName>
<ForeName>Valentin K</ForeName>
<Initials>VK</Initials>
<AffiliationInfo><Affiliation>Department of Internal Medicine (K.N.A., P.Z., S.S., H.L., E.A.J.) and Department of Neurobiology (E.A.J.), Yale University School of Medicine, New Haven, Connecticut; Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom (K.N.A.); Department of Neuroscience, Imaging and Clinical Sciences, University G.d'Annunzio of Chieti-Pescara, Chieti-Pescara, Italy (L.B.); Knopp Biosciences LLC, Pittsburgh, Pennsylvania (S.I.D., A.P.S., V.K.G.); and Biocurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts (P.J.S.S.).</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Jonas</LastName>
<ForeName>Elizabeth A</ForeName>
<Initials>EA</Initials>
<AffiliationInfo><Affiliation>Department of Internal Medicine (K.N.A., P.Z., S.S., H.L., E.A.J.) and Department of Neurobiology (E.A.J.), Yale University School of Medicine, New Haven, Connecticut; Division of Brain Sciences, Department of Medicine, Imperial College London, London, United Kingdom (K.N.A.); Department of Neuroscience, Imaging and Clinical Sciences, University G.d'Annunzio of Chieti-Pescara, Chieti-Pescara, Italy (L.B.); Knopp Biosciences LLC, Pittsburgh, Pennsylvania (S.I.D., A.P.S., V.K.G.); and Biocurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts (P.J.S.S.) Elizabeth.jonas@yale.edu.</Affiliation>
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<Acronym>NS</Acronym>
<Agency>NINDS NIH HHS</Agency>
<Country>United States</Country>
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<Acronym>NS</Acronym>
<Agency>NINDS NIH HHS</Agency>
<Country>United States</Country>
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<Acronym>NS</Acronym>
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<Grant><GrantID>R01 NS045876</GrantID>
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<Agency>NINDS NIH HHS</Agency>
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<Grant><GrantID>R56 NS064967</GrantID>
<Acronym>NS</Acronym>
<Agency>NINDS NIH HHS</Agency>
<Country>United States</Country>
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<Grant><GrantID>R01-NS064967</GrantID>
<Acronym>NS</Acronym>
<Agency>NINDS NIH HHS</Agency>
<Country>United States</Country>
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<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
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<ArticleDate DateType="Electronic"><Year>2014</Year>
<Month>10</Month>
<Day>20</Day>
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<MedlineTA>Mol Pharmacol</MedlineTA>
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<CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>J Exp Med. 2000 Oct 2;192(7):1001-14</RefSource>
<PMID Version="1">11015441</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Nat Cell Biol. 2011 Oct;13(10):1224-33</RefSource>
<PMID Version="1">21926988</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2169-74</RefSource>
<PMID Version="1">18250306</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Neurochem. 2004 Dec;91(5):1075-81</RefSource>
<PMID Version="1">15569251</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Ann N Y Acad Sci. 2008 Dec;1147:53-60</RefSource>
<PMID Version="1">19076430</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 1981 Feb 10;256(3):1362-9</RefSource>
<PMID Version="1">6450210</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Mol Biol Cell. 2005 May;16(5):2424-32</RefSource>
<PMID Version="1">15772159</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Circ J. 2013;77(5):1111-22</RefSource>
<PMID Version="1">23538482</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Cell. 2013 Jun 20;153(7):1510-25</RefSource>
<PMID Version="1">23791179</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>EMBO J. 2013 Aug 28;32(17):2362-76</RefSource>
<PMID Version="1">23900286</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Annu Rev Physiol. 2007;69:19-49</RefSource>
<PMID Version="1">17059356</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Cell Biol. 2001 Nov 26;155(5):725-31</RefSource>
<PMID Version="1">11724814</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Neurochem. 2006 Mar;96(5):1349-61</RefSource>
<PMID Version="1">16478527</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Cell Biol. 2011 Oct 17;195(2):263-76</RefSource>
<PMID Version="1">21987637</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 1992 Feb 15;267(5):2940-6</RefSource>
<PMID Version="1">1371109</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Proc Natl Acad Sci U S A. 2004 Sep 14;101(37):13590-5</RefSource>
<PMID Version="1">15342906</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Antioxid Redox Signal. 2015 Jan 10;22(2):93-108</RefSource>
<PMID Version="1">24787232</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 1991 Feb 25;266(6):3376-9</RefSource>
<PMID Version="1">1847371</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Neurosci. 2006 Jun 21;26(25):6851-62</RefSource>
<PMID Version="1">16793892</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>CNS Neurosci Ther. 2008 Fall;14(3):215-26</RefSource>
<PMID Version="1">18801114</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 2009 Dec 4;284(49):33982-8</RefSource>
<PMID Version="1">19801635</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Cell Biol. 2006 May 22;173(4):545-57</RefSource>
<PMID Version="1">16717129</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Cell Rep. 2013 Aug 15;4(3):413-9</RefSource>
<PMID Version="1">23891000</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Cell Biol. 1970 May;45(2):291-305</RefSource>
<PMID Version="1">4254678</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Circ Res. 2004 Mar 5;94(4):420-32</RefSource>
<PMID Version="1">15001541</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Proc Natl Acad Sci U S A. 2008 Mar 25;105(12):4892-7</RefSource>
<PMID Version="1">18347331</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 2003 Apr 4;278(14):12305-9</RefSource>
<PMID Version="1">12560333</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):10580-5</RefSource>
<PMID Version="1">24979777</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Neurosci. 2012 Jan 25;32(4):1233-43</RefSource>
<PMID Version="1">22279208</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Biochem Soc Trans. 2005 Nov;33(Pt 5):897-904</RefSource>
<PMID Version="1">16246006</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>FEBS Lett. 1989 Dec 18;259(1):137-43</RefSource>
<PMID Version="1">2480918</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Front Physiol. 2013 May 10;4:95</RefSource>
<PMID Version="1">23675351</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Physiol. 2003 Apr 15;548(Pt 2):425-38</RefSource>
<PMID Version="1">12588898</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Clin Pharmacol. 2011 Aug;51(8):1177-85</RefSource>
<PMID Version="1">20959524</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Front Physiol. 2014 Sep 17;5:355</RefSource>
<PMID Version="1">25278904</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):16823-7</RefSource>
<PMID Version="1">20847295</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Biochim Biophys Acta. 2014 Aug;1842(8):1267-72</RefSource>
<PMID Version="1">24055979</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Cell Biol. 2014 Mar 31;204(7):1087-98</RefSource>
<PMID Version="1">24687278</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Vis Exp. 2013;(75):e4394</RefSource>
<PMID Version="1">23685483</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Nat Neurosci. 2012 Apr;15(4):574-80</RefSource>
<PMID Version="1">22366758</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Front Neurol. 2013 Dec 11;4:199</RefSource>
<PMID Version="1">24376435</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Neural Transm Suppl. 2000;59:133-54</RefSource>
<PMID Version="1">10961426</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Ann N Y Acad Sci. 2008 Dec;1147:395-412</RefSource>
<PMID Version="1">19076459</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>FASEB J. 2006 Mar;20(3):556-8</RefSource>
<PMID Version="1">16407457</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Biochemistry. 1984 Aug 28;23(18):4140-3</RefSource>
<PMID Version="1">6237684</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Brain Res. 2012 Mar 29;1446:1-11</RefSource>
<PMID Version="1">22364637</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Neurochem. 1998 Jul;71(1):295-301</RefSource>
<PMID Version="1">9648878</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>FEBS Lett. 1998 Jun 12;429(2):201-6</RefSource>
<PMID Version="1">9650590</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>J Neurophysiol. 1997 Jul;78(1):281-94</RefSource>
<PMID Version="1">9242280</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Nature. 2004 Jan 22;427(6972):360-4</RefSource>
<PMID Version="1">14737170</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="Cites"><RefSource>Nat Rev Mol Cell Biol. 2008 Jan;9(1):47-59</RefSource>
<PMID Version="1">18097445</PMID>
</CommentsCorrections>
</CommentsCorrectionsList>
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The mitochondrial complex V-associated large-conductance inner membrane current is regulated by cyclosporine and dexpramipexole.

The mitochondrial complex V-associated large-conductance inner membrane current is regulated by cyclosporine and dexpramipexole.

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