Human mitochondrial carnitine acylcarnitine carrier: Molecular target of dietary bioactive polyphenols from sweet cherry (Prunus avium L.).

Lara Console, Nicola Giangregorio, Saverio Cellamare, Isabella Bolognino, Marino Palasciano, Cesare Indiveri, Giovanna Incampo, Sabrina Campana, Annamaria Tonazzi

Journal: Chemico-biological interactions 2019;307():179-185

PMID: 31063765

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Abstract

The effect of polyphenols, recognized as the principal antioxidant and beneficial molecules introduced with the diet, extracted from sweet cherry (Prunus avium L.) on the recombinant human mitochondrial carnitine/acylcarnitine transporter (CACT) has been studied in proteoliposomes. CACT transport activity, which was strongly impaired after oxidation by atmospheric O or HO due to the formation of a disulfide bridge between cysteines 136 and 155, was restored by externally added polyphenols. CACT reduction by polyphenols was time dependent. Spectroscopic analysis of polyphenolic extracts revealed eight most represented compounds in four cultivars. Molecular docking of CACT structural omology model with the most either abundant and arguably bio-available phenolic compound (trans 3-O-feruloyl-quinic acid) of the mix, is in agreement with the experimental data since it results located in the active site close to cysteine 136 at the bottom of the translocation aqueous cavity.

Address: Department DiBEST (Biologia, Ecologia, Scienze della Terra), Unit of Biochemistry and Molecular Biotechnology, Via Bucci 4C, University of Calabria, 87036, Arcavacata di Rende, Italy.; CNR-IBIOM (Institute of Biomembranes, Bioenergetics and Molecular Biotechnology), via Amendola 165/A, 70126, Bari, Italy; Department of Bioscience, Biotechnology and Biopharmaceutics, Via Orabona 4, 70125, University of Bari, Italy.; Dipartimento di Farmacia-Scienze del Farmaco, Via Orabona 4, 70125, University of Bari, Italy.; DiSSPA (Department of Soil, Plant and Food Science), University of Bari, via Amendola 165/A, 70126, Bari, Italy.; Department DiBEST (Biologia, Ecologia, Scienze della Terra), Unit of Biochemistry and Molecular Biotechnology, Via Bucci 4C, University of Calabria, 87036, Arcavacata di Rende, Italy; CNR-IBIOM (Institute of Biomembranes, Bioenergetics and Molecular Biotechnology), via Amendola 165/A, 70126, Bari, Italy.; Department of Bioscience, Biotechnology and Biopharmaceutics, Via Orabona 4, 70125, University of Bari, Italy.; CNR-IBIOM (Institute of Biomembranes, Bioenergetics and Molecular Biotechnology), via Amendola 165/A, 70126, Bari, Italy; Department of Bioscience, Biotechnology and Biopharmaceutics, Via Orabona 4, 70125, University of Bari, Italy. Electronic address: [email protected].

DOI: 10.1016/j.cbi.2019.05.006

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MeSH Terms: Binding Sites, Carnitine Acyltransferases, Humans, Hydrogen Peroxide, Mitochondria, Molecular Docking Simulation, Mutagenesis, Site-Directed, Oxidation-Reduction, Polyphenols, Protein Structure, Tertiary, Prunus avium, Recombinant Proteins, Spectrometry, Mass, Electrospray Ionization