The human uncoupling proteins 5 and 6 (UCP5/SLC25A14 and UCP6/SLC25A30) transport sulfur oxyanions, phosphate and dicarboxylates

Biochim Biophys Acta Bioenerg. 2019 Sep 1;1860(9):724-733. doi: 10.1016/j.bbabio.2019.07.010. Epub 2019 Jul 26.

Abstract

The human genome encodes 53 members of the solute carrier family 25 (SLC25), also called the mitochondrial carrier family. In this work, two members of this family, UCP5 (BMCP1, brain mitochondrial carrier protein 1 encoded by SLC25A14) and UCP6 (KMCP1, kidney mitochondrial carrier protein 1 encoded by SLC25A30) have been thoroughly characterized biochemically. They were overexpressed in bacteria, purified and reconstituted in phospholipid vesicles. Their transport properties and kinetic parameters demonstrate that UCP5 and UCP6 transport inorganic anions (sulfate, sulfite, thiosulfate and phosphate) and, to a lesser extent, a variety of dicarboxylates (e.g. malonate, malate and citramalate) and, even more so, aspartate and (only UCP5) glutamate and tricarboxylates. Both carriers catalyzed a fast counter-exchange transport and a very low uniport of substrates. Transport was saturable and inhibited by mercurials and other mitochondrial carrier inhibitors at various degrees. The transport affinities of UCP5 and UCP6 were higher for sulfate and thiosulfate than for any other substrate, whereas the specific activity of UCP5 was much higher than that of UCP6. It is proposed that a main physiological role of UCP5 and UCP6 is to catalyze the export of sulfite and thiosulfate (the H2S degradation products) from the mitochondria, thereby modulating the level of the important signal molecule H2S.

Keywords: Hydrogen sulfide; Membrane transport; Mitochondria; Mitochondrial carrier; UCP5; UCP6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anions / metabolism*
  • Biological Transport
  • Dicarboxylic Acids / metabolism*
  • Humans
  • Mitochondria / metabolism
  • Mitochondrial Uncoupling Proteins / metabolism*
  • Nerve Tissue Proteins / metabolism*
  • Phosphates / metabolism*
  • Sulfur / metabolism*

Substances

  • Anions
  • Dicarboxylic Acids
  • Mitochondrial Uncoupling Proteins
  • Nerve Tissue Proteins
  • Phosphates
  • SLC25A14 protein, human
  • Sulfur