Mitochondrial uncoupling protein 4 (UCP4) is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''SLC25A27''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
Tissue distribution
''SLC25A27'' transcripts are detected exclusively in brain tissue.
Expression of UCP4 is developmentally regulated and influenced by environmental conditions. This brain-specific expression pattern distinguishes UCP4 from other uncoupling proteins, which are found in a wider range of tissues.
Structure
UCP4 shares the typical structural features of the MACP family, including three homologous protein domains that span the inner mitochondrial membrane. However, reconstituted UCP4 has been observed to adopt a conformation distinct from other uncoupling proteins, suggesting potential functional or regulatory differences.
Function
Mitochondrial uncoupling proteins (UCPs) are part of the mitochondrial anion carrier protein (MACP) family. They mediate proton leak across the inner mitochondrial membrane, uncoupling oxidative phosphorylation from ATP synthesis and dissipating energy as heat. This process lowers the mitochondrial membrane potential and contributes to thermogenesis and regulation of reactive oxygen species.
UCPs facilitate the transport of anions from the mitochondrial matrix to the intermembrane space, and the reverse flow of protons. Their activity is modulated by various ligands; for example, UCP4 is activated by fatty acids and inhibited by purine nucleotides.
Homologs in ''Drosophila''
In ''
Drosophila melanogaster
''Drosophila melanogaster'' is a species of fly (an insect of the Order (biology), order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly", "pomace fly" ...
'', four UCP homologs—DmUCP4A, DmUCP4B, DmUCP4C, and DmUCP5—have been identified based on sequence similarity to mammalian UCP4 and UCP5. Among these, DmUCP4A has been shown to protect against mitochondrial dysfunction in models of Parkinson’s disease by increasing mitochondrial membrane potential and enhancing ATP synthesis.
DmUCP4A functions as an aspartate transporter, catalyzing the unidirectional movement of aspartate from mitochondria to the cytosol. This transport is saturable, inhibited by mercurial compounds and other mitochondrial carrier inhibitors, and is not coupled to proton exchange. In ''Drosophila'', cytosolic aspartate is essential for protein and nucleotide biosynthesis, as well as the production of β-alanine and N-acetylaspartate—metabolites important for neuronal function.
See also
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Solute carrier family
The solute carrier (SLC) group of membrane transport proteins include over 400 members organized into 66 families. Most members of the SLC group are located in the cell membrane. The SLC gene nomenclature system was originally proposed by the HUGO ...
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Uncoupling protein
An uncoupling protein (UCP) is a mitochondrial inner membrane protein that is a regulated proton channel or transporter. An uncoupling protein is thus capable of dissipating the proton gradient generated by NADH-powered pumping of protons from the ...
References
Further reading
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Solute carrier family
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