Abstract

Heme is an essential molecule in many biological processes, such as transport and storage of oxygen and electron transfer as well as a structural component of hemoproteins. Defects of heme biosynthesis in developing erythroblasts have profound medical implications, as represented by sideroblastic anemia. The synthesis of heme requires the uptake of glycine into the mitochondrial matrix where glycine is condensed with succinyl coenzyme A to yield ?-aminolevulinic acid. Herein we describe the biochemical and molecular characterization of yeast Hem25p and human SLC25A38, providing evidence that they are mitochondrial carriers for glycine. In particular, the hem25? mutant manifests a defect in the biosynthesis of ?-aminolevulinic acid and displays reduced levels of downstream heme and mitochondrial cytochromes. The observed defects are rescued by complementation with yeast HEM25 or human SLC25A38 genes. Our results identify new proteins in the heme biosynthetic pathway and demonstrate that Hem25p and its human orthologue SLC25A38 are the main mitochondrial glycine transporters required for heme synthesis, providing definitive evidence of their previously proposed glycine transport function. Furthermore, our work may suggest new therapeutic approaches for the treatment of congenital sideroblastic anemia.

Autore Pugliese

• Paradies Eleonora

Tutti gli autori

• Lunetti P.; Damiano F.; De Benedetto G.; Siculella L.; Pennetta A.; Muto L.; Paradies E.; Marobbio C.M.T.; Dolce V.; Capobianco L.

Titolo volume/Rivista

The Journal of biological chemistry

Anno di pubblicazione

2016

ISSN

0021-9258

ISBN

Non Disponibile

Numero di citazioni Wos

Nessuna citazione

Ultimo Aggiornamento Citazioni

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Numero di citazioni Scopus

Non Disponibile

Ultimo Aggiornamento Citazioni

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Settori ERC

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Codici ASJC

Non Disponibile