Cargando…

Drosophila melanogaster Uncoupling Protein-4A (UCP4A) Catalyzes a Unidirectional Transport of Aspartate

Uncoupling proteins (UCPs) form a distinct subfamily of the mitochondrial carrier family (MCF) SLC25. Four UCPs, DmUCP4A-C and DmUCP5, have been identified in Drosophila melanogaster on the basis of their sequence homology with mammalian UCP4 and UCP5. In a Parkinson’s disease model, DmUCP4A showed...

Descripción completa

Detalles Bibliográficos
Autores principales: Lunetti, Paola, Gorgoglione, Ruggiero, Curcio, Rosita, Marra, Federica, Pignataro, Antonella, Vozza, Angelo, Riley, Christopher L., Capobianco, Loredana, Palmieri, Luigi, Dolce, Vincenza, Fiermonte, Giuseppe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8834685/
https://www.ncbi.nlm.nih.gov/pubmed/35162943
http://dx.doi.org/10.3390/ijms23031020
_version_ 1784649245226172416
author Lunetti, Paola
Gorgoglione, Ruggiero
Curcio, Rosita
Marra, Federica
Pignataro, Antonella
Vozza, Angelo
Riley, Christopher L.
Capobianco, Loredana
Palmieri, Luigi
Dolce, Vincenza
Fiermonte, Giuseppe
author_facet Lunetti, Paola
Gorgoglione, Ruggiero
Curcio, Rosita
Marra, Federica
Pignataro, Antonella
Vozza, Angelo
Riley, Christopher L.
Capobianco, Loredana
Palmieri, Luigi
Dolce, Vincenza
Fiermonte, Giuseppe
author_sort Lunetti, Paola
collection PubMed
description Uncoupling proteins (UCPs) form a distinct subfamily of the mitochondrial carrier family (MCF) SLC25. Four UCPs, DmUCP4A-C and DmUCP5, have been identified in Drosophila melanogaster on the basis of their sequence homology with mammalian UCP4 and UCP5. In a Parkinson’s disease model, DmUCP4A showed a protective role against mitochondrial dysfunction, by increasing mitochondrial membrane potential and ATP synthesis. To date, DmUCP4A is still an orphan of a biochemical function, although its possible involvement in mitochondrial uncoupling has been ruled out. Here, we show that DmUCP4A expressed in bacteria and reconstituted in phospholipid vesicles catalyzes a unidirectional transport of aspartate, which is saturable and inhibited by mercurials and other mitochondrial carrier inhibitors to various degrees. Swelling experiments carried out in yeast mitochondria have demonstrated that the unidirectional transport of aspartate catalyzed by DmUCP4 is not proton-coupled. The biochemical function of DmUCP4A has been further confirmed in a yeast cell model, in which growth has required an efflux of aspartate from mitochondria. Notably, DmUCP4A is the first UCP4 homolog from any species to be biochemically characterized. In Drosophila melanogaster, DmUCP4A could be involved in the transport of aspartate from mitochondria to the cytosol, in which it could be used for protein and nucleotide synthesis, as well as in the biosynthesis of ß-alanine and N-acetylaspartate, which play key roles in signal transmission in the central nervous system.
format Online
Article
Text
id pubmed-8834685
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-88346852022-02-12 Drosophila melanogaster Uncoupling Protein-4A (UCP4A) Catalyzes a Unidirectional Transport of Aspartate Lunetti, Paola Gorgoglione, Ruggiero Curcio, Rosita Marra, Federica Pignataro, Antonella Vozza, Angelo Riley, Christopher L. Capobianco, Loredana Palmieri, Luigi Dolce, Vincenza Fiermonte, Giuseppe Int J Mol Sci Article Uncoupling proteins (UCPs) form a distinct subfamily of the mitochondrial carrier family (MCF) SLC25. Four UCPs, DmUCP4A-C and DmUCP5, have been identified in Drosophila melanogaster on the basis of their sequence homology with mammalian UCP4 and UCP5. In a Parkinson’s disease model, DmUCP4A showed a protective role against mitochondrial dysfunction, by increasing mitochondrial membrane potential and ATP synthesis. To date, DmUCP4A is still an orphan of a biochemical function, although its possible involvement in mitochondrial uncoupling has been ruled out. Here, we show that DmUCP4A expressed in bacteria and reconstituted in phospholipid vesicles catalyzes a unidirectional transport of aspartate, which is saturable and inhibited by mercurials and other mitochondrial carrier inhibitors to various degrees. Swelling experiments carried out in yeast mitochondria have demonstrated that the unidirectional transport of aspartate catalyzed by DmUCP4 is not proton-coupled. The biochemical function of DmUCP4A has been further confirmed in a yeast cell model, in which growth has required an efflux of aspartate from mitochondria. Notably, DmUCP4A is the first UCP4 homolog from any species to be biochemically characterized. In Drosophila melanogaster, DmUCP4A could be involved in the transport of aspartate from mitochondria to the cytosol, in which it could be used for protein and nucleotide synthesis, as well as in the biosynthesis of ß-alanine and N-acetylaspartate, which play key roles in signal transmission in the central nervous system. MDPI 2022-01-18 /pmc/articles/PMC8834685/ /pubmed/35162943 http://dx.doi.org/10.3390/ijms23031020 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lunetti, Paola
Gorgoglione, Ruggiero
Curcio, Rosita
Marra, Federica
Pignataro, Antonella
Vozza, Angelo
Riley, Christopher L.
Capobianco, Loredana
Palmieri, Luigi
Dolce, Vincenza
Fiermonte, Giuseppe
Drosophila melanogaster Uncoupling Protein-4A (UCP4A) Catalyzes a Unidirectional Transport of Aspartate
title Drosophila melanogaster Uncoupling Protein-4A (UCP4A) Catalyzes a Unidirectional Transport of Aspartate
title_full Drosophila melanogaster Uncoupling Protein-4A (UCP4A) Catalyzes a Unidirectional Transport of Aspartate
title_fullStr Drosophila melanogaster Uncoupling Protein-4A (UCP4A) Catalyzes a Unidirectional Transport of Aspartate
title_full_unstemmed Drosophila melanogaster Uncoupling Protein-4A (UCP4A) Catalyzes a Unidirectional Transport of Aspartate
title_short Drosophila melanogaster Uncoupling Protein-4A (UCP4A) Catalyzes a Unidirectional Transport of Aspartate
title_sort drosophila melanogaster uncoupling protein-4a (ucp4a) catalyzes a unidirectional transport of aspartate
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8834685/
https://www.ncbi.nlm.nih.gov/pubmed/35162943
http://dx.doi.org/10.3390/ijms23031020
work_keys_str_mv AT lunettipaola drosophilamelanogasteruncouplingprotein4aucp4acatalyzesaunidirectionaltransportofaspartate
AT gorgoglioneruggiero drosophilamelanogasteruncouplingprotein4aucp4acatalyzesaunidirectionaltransportofaspartate
AT curciorosita drosophilamelanogasteruncouplingprotein4aucp4acatalyzesaunidirectionaltransportofaspartate
AT marrafederica drosophilamelanogasteruncouplingprotein4aucp4acatalyzesaunidirectionaltransportofaspartate
AT pignataroantonella drosophilamelanogasteruncouplingprotein4aucp4acatalyzesaunidirectionaltransportofaspartate
AT vozzaangelo drosophilamelanogasteruncouplingprotein4aucp4acatalyzesaunidirectionaltransportofaspartate
AT rileychristopherl drosophilamelanogasteruncouplingprotein4aucp4acatalyzesaunidirectionaltransportofaspartate
AT capobiancoloredana drosophilamelanogasteruncouplingprotein4aucp4acatalyzesaunidirectionaltransportofaspartate
AT palmieriluigi drosophilamelanogasteruncouplingprotein4aucp4acatalyzesaunidirectionaltransportofaspartate
AT dolcevincenza drosophilamelanogasteruncouplingprotein4aucp4acatalyzesaunidirectionaltransportofaspartate
AT fiermontegiuseppe drosophilamelanogasteruncouplingprotein4aucp4acatalyzesaunidirectionaltransportofaspartate