FEBS Lett. 2023 Dec 06.
Francesco De Leonardis,
Amer Ahmed,
Angelo Vozza,
Loredana Capobianco,
Christopher L Riley,
Simona Nicole Barile,
Daria Di Molfetta,
Stefano Tiziani,
John DiGiovanni,
Luigi Palmieri,
Vincenza Dolce,
Giuseppe Fiermonte.
Since its discovery, a major debate about mitochondrial uncoupling protein 3 (UCP3) has been whether its metabolic actions result primarily from mitochondrial inner membrane proton transport, a process that decreases respiratory efficiency and ATP synthesis. However, UCP3 expression and activity are induced by conditions that would seem at odds with inefficient "uncoupled" respiration, including fasting and exercise. Here we demonstrate that the bacterially expressed human UCP3, reconstituted into liposomes, catalyses a strict exchange of aspartate, malate, oxaloacetate, and phosphate. The R282Q mutation abolishes the transport activity of the protein. Although the substrate specificity and inhibitor sensitivity of UCP3 display similarity with that of its close homolog UCP2, the two proteins significantly differ in their transport mode and kinetic constants.
Keywords: amino acid transport; anion transport; bioenergetics; mitochondrial metabolism; mitochondrial transport; uncoupling protein