Evidence map›Paper›PMID 29212043›Full record

ArticleBiochimica et biophysica acta. Biomembranes2018

Inhibition of mitochondrial UCP1 and UCP3 by purine nucleotides and phosphate.

Gabriel Macher, Melanie Koehler, Anne Rupprecht, Jürgen Kreiter, Peter Hinterdorfer, Elena E Pohl

Open access · greenAbstract readComparative Study
In one paragraph

Article in Biochimica et biophysica acta. Biomembranes, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.6field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 45 citations in OpenAlex.

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  16. Molecular Dynamics Simulations of Mitochondrial Uncoupling Protein 2.International journal of molecular sciences · 2021
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  18. International journal of molecular sciences · 2020
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Gabriel MacherInstitute of Physiology, Pathophysiology and Biophysics, University of Veterinary Medicine, Vienna, Austria.
Melanie KoehlerInstitute of Biophysics, Johannes Kepler University, Linz, Austria.
Anne RupprechtInstitute of Physiology, Pathophysiology and Biophysics, University of Veterinary Medicine, Vienna, Austria.
Jürgen KreiterInstitute of Physiology, Pathophysiology and Biophysics, University of Veterinary Medicine, Vienna, Austria.
Peter HinterdorferInstitute of Biophysics, Johannes Kepler University, Linz, Austria.
Elena E PohlInstitute of Physiology, Pathophysiology and Biophysics, University of Veterinary Medicine, Vienna, Austria. Electronic address: elena.pohl@vetmeduni.ac.at.
University of Veterinary Medicine Vienna · ATJohannes Kepler University of Linz · AT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mitochondrial membrane uncoupling protein 3 (UCP3) is not only expressed in skeletal muscle and heart, but also in brown adipose tissue (BAT) alongside UCP1, which facilitates a proton leak to support non-shivering thermogenesis. In contrast to UCP1, the transport function and molecular mechanism of UCP3 regulation are poorly investigated, although it is generally agreed upon that UCP3, analogous to UCP1, transports protons, is activated by free fatty acids (FFAs) and is inhibited by purine nucleotides (PNs). Because the presence of two similar uncoupling proteins in BAT is surprising, we hypothesized that UCP1 and UCP3 are differently regulated, which may lead to differences in their functions. By combining atomic force microscopy and electrophysiological measurements of recombinant proteins reconstituted in planar bilayer membranes, we compared the level of protein activity with the bond lifetimes between UCPs and PNs. Our data revealed that, in contrast to UCP1, UCP3 can be fully inhibited by all PNs and IC50 increases with a decrease in PN-phosphorylation. Experiments with mutant proteins demonstrated that the conserved arginines in the PN-binding pocket are involved in the inhibition of UCP1 and UCP3 to different extents. Fatty acids compete with all PNs bound to UCP1, but only with ATP bound to UCP3. We identified phosphate as a novel inhibitor of UCP3 and UCP1, which acts independently of PNs. The differences in molecular mechanisms of the inhibition between the highly homologous transporters UCP1 and UCP3 indicate that UCP3 has adapted to fulfill a different role and possibly another transport function in BAT.

Indexed as

Adenine NucleotidesAnimalsArginineBinding, CompetitiveFatty AcidsLipid BilayersLiposomesMiceMicroscopy, Atomic ForceMutagenesis, Site-DirectedPhosphatesProtonsRecombinant ProteinsUncoupling Protein 1Uncoupling Protein 3Adenine NucleotidesArginineFatty AcidsLipid BilayersLiposomesPhosphatesProtonsRecombinant ProteinsUcp1 protein, mouseUcp3 protein, mouseUncoupling Protein 1Uncoupling Protein 3Arachidonic acidAtomic force microscopyConductance of planar bilayer membraneMitochondrial uncoupling proteinsMolecular mechanism of protein inhibitionPurine nucleotide binding site

Identifiers

PMID29212043
PMCPMC6118327
OpenAlexW2773801698

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.