Abstract

Mitochondrial carriers are a superfamily of transport proteins that, with a few exceptions, are found in the inner membranes of mitochondria. They shuttle metabolites, nucleotides and cofactors through this membrane, and thereby connect and/or regulate cytoplasm and matrix functions. Although several members of this family have been characterized, the functions of many others still remains unknown. For instance, the carrier responsible for coenzyme A (COA) transport into mitochondria has not yet been identified. CoA is an essential cytosolic-synthesized cofactor required in many intra-mitochondrial pathways, such as Krebs cycle, fatty acid β-oxidation and fatty acid synthesis (for the activation of mitochondrial ACP). In this work, we have identified SLC25A42 as the human gene responsible for the transport of CoA into mitochondria. The protein encoded by SLC25A42 is localized in the inner mitochondrial membrane and is ubiquitously expressed, aIthough at different levels. Its functional characterization has been carried out on bacterially expressed protein, upon its purification and reconstitution into phospholipid vesicles. In the reconstituted system the recombinant protein, exhibited high transport affinity for CoA, dephospho-CoA, ADP and adenosine 3',5'-diphosphate (PAP). The main physiological role of SLC25A42 is to import CoA into mitochondria in exchange for intra-mitochondrial adenine nucleotides and/or PAP. The export of PAP out of the mitochondria is crucial, since the catabolism of this cytotoxic molecule, produced in the organelles by the transfer of the 4'-phosphopantetheine prosthetic group of CoA to ACP, takes place in the cytosol. This is the first time that a mitochondrial carrier for CoA and PAP has been identified and characterized biochemically.

Autore Pugliese

• Marobbio Carlo Marya , Fiermonte Giuseppe

Tutti gli autori

• MAROBBIO C.M.;FIERMONTE G.

Titolo volume/Rivista

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Anno di pubblicazione

2010

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Settori ERC

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Codici ASJC

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