Kreiter, J.; Tyschuk, T.; Pohl, E.E. Uncoupling Protein 3 Catalyzes the Exchange of C4 Metabolites Similar to UCP2. Biomolecules2024, 14, 21.
Kreiter, J.; Tyschuk, T.; Pohl, E.E. Uncoupling Protein 3 Catalyzes the Exchange of C4 Metabolites Similar to UCP2. Biomolecules 2024, 14, 21.
Kreiter, J.; Tyschuk, T.; Pohl, E.E. Uncoupling Protein 3 Catalyzes the Exchange of C4 Metabolites Similar to UCP2. Biomolecules2024, 14, 21.
Kreiter, J.; Tyschuk, T.; Pohl, E.E. Uncoupling Protein 3 Catalyzes the Exchange of C4 Metabolites Similar to UCP2. Biomolecules 2024, 14, 21.
Abstract
Uncoupling protein 3 (UCP3) belongs to the mitochondrial carrier protein superfamily SLC25 and is abundant in brown adipose tissue (BAT), heart and muscles. Unlike UCP1, which is localized in BAT and involved in non-shievering thermogenesis, its biological function is under dispute. The expression of UCP3 in tissues mainly dependent on fatty acid oxidation suggests its involvement in cellular metabolism and has drawn attention to its possible transport function beyond the transport of protons in the presence of fatty acids. Based on the high homology between UCP2 and UCP3, we hypothesized that UCP3 transports C4 metabolites similar to UCP2. To test this, we measured the transport of substrates against phosphate (32Pi) in proteoliposomes reconstituted with recombinant murine UCP3. We found that UCP3 mainly transports aspartate and sulfate but also malate, malonate, oxaloacetate and succinate. The transport rates calculated from the exchange of 32Pi against extraliposomal aspartate and sulfate were 23.9 ± 5.8 and 17.5 ± 5.1 µmol/min/mg, respectively. Using site-directed mutagenesis we revealed that mutation of R84 resulted in impaired aspartate/phosphate exchange, demonstrating its critical role in substrate transport. Difference in substrate preference between UCP2 and UCP3 may be explained by their different tissue expression pattern and biological function in these tissues.
Keywords
SLC25 protein family; substrate transport; aspartate; malonate; malate; sulfate
Subject
Biology and Life Sciences, Biophysics
Copyright:
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