Mitochondrial uncoupling protein 4 is a protein that in humans is encoded by the SLC25A27gene.[5][6][7]
Mitochondrial uncoupling proteins (UCP) are members of the larger family of mitochondrial anion carrier proteins (MACP). UCPs separate oxidative phosphorylation from ATP synthesis with energy dissipated as heat, also referred to as the mitochondrial proton leak. UCPs facilitate the transfer of anions from the inner to the outer mitochondrial membrane and the return transfer of protons from the outer to the inner mitochondrial membrane. They also reduce the mitochondrial membrane potential in mammalian cells. Tissue specificity occurs for the different UCPs and the exact methods of how UCPs transfer H+/OH- are not known. UCPs contain the three homologous protein domains of MACPs. Transcripts of this gene are detected only in brain tissue and are specifically modulated by various environmental conditions.[7] Recently, the proton transport activity of UCP4 has also been shown to be activated by fatty acids and inhibited by purine nucleotides.[8] In addition, reconstituted UCP4 exhibited a distinct conformation, compared to other UCPs in the family.[9]
In Drosophila melanogaster, four UCPs—DmUCP4A-C and DmUCP5—have been identified based on their sequence homology with mammalian UCP4 and UCP5. Notably, DmUCP4A has been shown to protect against mitochondrial dysfunction in Parkinson's disease models by increasing mitochondrial membrane potential and ATP synthesis. Recent studies have demonstrated that DmUCP4A functions as an aspartate transporter, facilitating the unidirectional movement of aspartate from mitochondria to the cytosol. This transport is saturable and inhibited by mercurials and other mitochondrial carrier inhibitors, and it is not proton-coupled. In Drosophila, cytosolic aspartate is essential for protein and nucleotide synthesis, as well as the biosynthesis of β-alanine and N-acetylaspartate, which are crucial for signal transmission in the central nervous system.[10]
^Hoang T, Smith MD, Jelokhani-Niaraki M (2012). "Toward Understanding the Mechanism of Ion Transport Activity of Neuronal Uncoupling Proteins UCP2, UCP4, and UCP5". Biochemistry. 51 (19): 4004–14. doi:10.1021/bi3003378. PMID22524567.
^Ivanova M, Hoang T, McSorly FR, Krnac G, Smith MD, Jelokhani-Niaraki M (2010). "A comparative study on conformation and ligand binding of the neuronal uncoupling proteins". Biochemistry. 49 (3): 512–21. doi:10.1021/bi901742g. PMID20000716.
Yasuno K, Ando S, Misumi S, et al. (2007). "Synergistic association of mitochondrial uncoupling protein (UCP) genes with schizophrenia". Am. J. Med. Genet. B Neuropsychiatr. Genet. 144 (2): 250–3. doi:10.1002/ajmg.b.30443. PMID17066476. S2CID30129988.
