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

Autor:	Paola Lunetti, Ruggiero Gorgoglione, Rosita Curcio, Federica Marra, Antonella Pignataro, Angelo Vozza, Christopher L. Riley, Loredana Capobianco, Luigi Palmieri, Vincenza Dolce, Giuseppe Fiermonte
Přispěvatelé:	Lunetti, Paola, Gorgoglione, Ruggiero, Curcio, Rosita, Marra, Federica, Pignataro, Antonella, Vozza, Angelo, Riley, Christopher L., Capobianco, Loredana, Palmieri, Luigi, Dolce, Vincenza, Fiermonte, Giuseppe
Rok vydání:	2022
Předmět:	QH301-705.5 ß-alanine Organic Chemistry uncoupling proteins uncoupling proteins DmUCP4A mitochondrial transporters aspartate transport alanine biogenic amines metabolism Parkinson’s disease CG6492 mitochondrial carrier family N-acetylaspartate DmUCP4A mitochondrial transporters aspartate transport biogenic amines metabolism Parkinson’s disease CG6492 mitochondrial carrier family N-acetylaspartate General Medicine Catalysis Computer Science Applications Inorganic Chemistry Chemistry Biology (General) Physical and Theoretical Chemistry QD1-999 Molecular Biology Spectroscopy
Zdroj:	International Journal of Molecular Sciences, Vol 23, Iss 1020, p 1020 (2022) International Journal of Molecular Sciences; Volume 23; Issue 3; Pages: 1020
ISSN:	1422-0067
DOI:	10.3390/ijms23031020
Popis:	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.
Databáze:	OpenAIRE
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