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Human mitochondrial uncoupling protein 3 functions as a metabolite transporter
Francesco De Leonardis1, Amer Ahmed1, Angelo Vozza1
1Department of Bioscience, Biotechnology and Environment, University of Bari, Italy.
FEBS Letters
|December 7, 2023
Summary
Mitochondrial uncoupling protein 3 (UCP3) may not primarily transport protons. This study shows UCP3 facilitates anion exchange, suggesting a different role in cellular metabolism beyond just reducing respiratory efficiency.
Area of Science:
- Mitochondrial physiology
- Protein biochemistry
- Metabolic regulation
Background:
- Mitochondrial uncoupling protein 3 (UCP3) function is debated, with a focus on proton transport and its impact on ATP synthesis.
- UCP3 expression increases during fasting and exercise, conditions seemingly contradictory to inefficient respiration.
Purpose of the Study:
- To investigate the precise transport activity of human UCP3.
- To determine if UCP3 functions as a proton transporter or facilitates other molecular exchanges.
Main Methods:
- Bacterial expression and purification of human UCP3.
- Reconstitution of UCP3 into liposomes for transport assays.
- Assessment of transport activity using specific substrates and a mutant protein (R282Q).
Main Results:
- Reconstituted UCP3 demonstrated strict exchange activity for anions: aspartate, malate, sulfate, and phosphate.
- The R282Q mutation completely abolished UCP3's transport function.
- UCP3 shares substrate and inhibitor similarities with UCP2 but differs in transport mechanism and kinetics.
Conclusions:
- Human UCP3 functions as an anion transporter, not primarily as a proton transporter.
- This finding re-evaluates the role of UCP3 in cellular metabolism and energy regulation.
- UCP3's distinct transport mode differentiates it from UCP2, highlighting specific physiological roles.
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