Abstract

Themitochondrial carnitine/acylcarnitine carrier (CAC) is essential for cellmetabolism since itcatalyzes the transport of acylcarnitines into mitochondria allowing the ?-oxidation of fatty acids. CACfunctional and structural properties have been characterized. Cys residues which could form disulfidessuggest the involvement of CAC in redox switches.Methods: The effect of GSH and GSSG on the [3H]-carnitine/carnitine antiport catalyzed by the CAC inproteoliposomes has been studied. The Cys residues involved in the redox switch have been identified bysite-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 effectwas observed on the recombinant CAC. The presence of glutaredoxin-1 (Grx1) accelerated the GSH activationof the recombinant CAC. The effect was more evident at 37 °C. GSSG led to transport inhibition which wasreversed by dithioerythritol (DTE). The effects of GSH and GSSG were studied on CAC Cys-mutants. CAC lackingC136 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 responsiblefor the regulation which occurs through glutathionylation.General significance: CAC is sensitive to the redox state of the cell switching between oxidized and reduced formsin response to variation of GSSG and GSH concentrations.

Autore Pugliese

• Giangregorio Nicola

Tutti gli autori

• Giangregorio N.; Palmieri F.; Indiveri C.

Titolo volume/Rivista

Biochimica et biophysica acta. G, General subjects

Anno di pubblicazione

2013

ISSN

0304-4165

ISBN

Non Disponibile

Numero di citazioni Wos

Nessuna citazione

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Numero di citazioni Scopus

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Settori ERC

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Codici ASJC

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