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Glutathione controls the redox state of the mitochondrial carnitine/acylcarnitine carrier Cys residues by glutathionylation. (Articolo in rivista)
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- Glutathione controls the redox state of the mitochondrial carnitine/acylcarnitine carrier Cys residues by glutathionylation. (Articolo in rivista) (literal)
- Anno
- 2013-01-01T00:00:00+01:00 (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
- 10.1016/j.bbagen.2013.08.003 (literal)
- Alternative label
Giangregorio N, Palmieri F, Indiveri C. (2013)
Glutathione controls the redox state of the mitochondrial carnitine/acylcarnitine carrier Cys residues by glutathionylation.
in Biochimica et biophysica acta. G, General subjects (Print)
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- Giangregorio N, Palmieri F, Indiveri C. (literal)
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- CNR Institute of Biomembranes and Bioenergetics, via Amendola 165/A, 70126 Bari, Italy
Department of Bioscience, Biotechnology and Biopharmaceutics, University of Bari, Italy
Department BEST (Biologia, Ecologia, Scienze della Terra) Unit of Biochemistry and Molecular Biotechnology, University of Calabria, 87036 Arcavacata di Rende, Italy (literal)
- Titolo
- Glutathione controls the redox state of the mitochondrial carnitine/acylcarnitine carrier Cys residues by glutathionylation. (literal)
- Abstract
- Background: Themitochondrial carnitine/acylcarnitine carrier (CAC) is essential for cellmetabolism since it
catalyzes the transport of acylcarnitines into mitochondria allowing the ?-oxidation of fatty acids. CAC
functional and structural properties have been characterized. Cys residues which could form disulfides
suggest the involvement of CAC in redox switches.
Methods: The effect of GSH and GSSG on the [3H]-carnitine/carnitine antiport catalyzed by the CAC in
proteoliposomes has been studied. The Cys residues involved in the redox switch have been identified by
site-directed mutagenesis. Glutathionylated CAC has been assessed by glutathionyl-protein specific antibody.
Results: GSH led to increase of transport activity of the CAC extracted from liver mitochondria. A similar effect
was observed on the recombinant CAC. The presence of glutaredoxin-1 (Grx1) accelerated the GSH activation
of the recombinant CAC. The effect was more evident at 37 °C. GSSG led to transport inhibition which was
reversed by dithioerythritol (DTE). The effects of GSH and GSSG were studied on CAC Cys-mutants. CAC lacking
C136 and C155 was insensitive to both reagents. Mutants containing these two Cys responded as the wild-type.
Anti-glutathionyl antibody revealed the formation of glutathionylated CAC.
Conclusions: CAC is redox-sensitive and it is regulated by the GSH/GSSG couple. C136 and C155 are responsible
for the regulation which occurs through glutathionylation.
General significance: CAC is sensitive to the redox state of the cell switching between oxidized and reduced forms
in response to variation of GSSG and GSH concentrations. (literal)
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