Evidence map›Paper›PMID 25535394›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

Superresolution microscopy reveals spatial separation of UCP4 and F0F1-ATP synthase in neuronal mitochondria.

Enrico Klotzsch, Alina Smorodchenko, Lukas Löfler, Rudolf Moldzio, Elena Parkinson, Gerhard J Schütz, Elena E Pohl

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

38 citing papers in PubMed, 57 citations in OpenAlex.

  1. Proton wave propagation along collagen fibers.European biophysics journal : EBJ · 2026
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  2. Article
  3. Glycolipids slow interfacial proton migration while preserving surface proton retention.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
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  16. Light Microscopy of Mitochondria at the Nanoscale.Annual review of biophysics · 2020
    Review
  17. Article
  18. Review
  19. Intracellular quality control of mitochondrial DNA: evidence and limitations.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2020
    Review
  20. Review
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

7 authors at 2 institutions in 1 country.

Enrico KlotzschInstitute of Applied Physics, Vienna University of Technology, A-1040 Vienna, Austria; and enricoklotzsch@gmail.com schuetz@iap.tuwien.ac.at elena.pohl@vetmeduni.ac.at.
Alina SmorodchenkoInstitutes of Physiology, Pathophysiology and Biophysics and.
Lukas LöflerInstitute of Applied Physics, Vienna University of Technology, A-1040 Vienna, Austria; and.
Rudolf MoldzioMedical Biochemistry, University of Veterinary Medicine, A-1210 Vienna, Austria.
Elena ParkinsonInstitute of Applied Physics, Vienna University of Technology, A-1040 Vienna, Austria; and.
Gerhard J SchützInstitute of Applied Physics, Vienna University of Technology, A-1040 Vienna, Austria; and enricoklotzsch@gmail.com schuetz@iap.tuwien.ac.at elena.pohl@vetmeduni.ac.at.
Elena E PohlInstitutes of Physiology, Pathophysiology and Biophysics and enricoklotzsch@gmail.com schuetz@iap.tuwien.ac.at elena.pohl@vetmeduni.ac.at.
TU Wien · ATUniversity of Veterinary Medicine Vienna · AT

Funding

Austrian Science Fund FWF P 25123
6 · The paper itself

Abstract

Because different proteins compete for the proton gradient across the inner mitochondrial membrane, an efficient mechanism is required for allocation of associated chemical potential to the distinct demands, such as ATP production, thermogenesis, regulation of reactive oxygen species (ROS), etc. Here, we used the superresolution technique dSTORM (direct stochastic optical reconstruction microscopy) to visualize several mitochondrial proteins in primary mouse neurons and test the hypothesis that uncoupling protein 4 (UCP4) and F0F1-ATP synthase are spatially separated to eliminate competition for the proton motive force. We found that UCP4, F0F1-ATP synthase, and the mitochondrial marker voltage-dependent anion channel (VDAC) have various expression levels in different mitochondria, supporting the hypothesis of mitochondrial heterogeneity. Our experimental results further revealed that UCP4 is preferentially localized in close vicinity to VDAC, presumably at the inner boundary membrane, whereas F0F1-ATP synthase is more centrally located at the cristae membrane. The data suggest that UCP4 cannot compete for protons because of its spatial separation from both the proton pumps and the ATP synthase. Thus, mitochondrial morphology precludes UCP4 from acting as an uncoupler of oxidative phosphorylation but is consistent with the view that UCP4 may dissipate the excessive proton gradient, which is usually associated with ROS production.

Indexed as

AnimalsMembrane Potential, MitochondrialMembrane Transport ProteinsMiceMicroscopyMitochondriaMitochondrial MembranesMitochondrial Uncoupling ProteinsNeuronsProtonsProton-Translocating ATPasesVoltage-Dependent Anion ChannelsMembrane Transport ProteinsMitochondrial Uncoupling ProteinsProtonsProton-Translocating ATPasesSlc25a27 protein, mouseVoltage-Dependent Anion Channelsdirect stochastic optical reconstruction microscopymitochondrial membrane proteinsproton diffusionreactive oxygen speciesuncoupling

Identifiers

PMID25535394
PMCPMC4291679
OpenAlexW2011015136

What OpenQuestion holds

Textmetadata
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.