Evidence map›Paper›PMID 27532055›Full record

ArticleScience advances2016

POLRMT regulates the switch between replication primer formation and gene expression of mammalian mtDNA.

Inge Kühl, Maria Miranda, Viktor Posse, Dusanka Milenkovic, Arnaud Mourier, Stefan J Siira, Nina A Bonekamp, Ulla Neumann, Aleksandra Filipovska, Paola Loguercio Polosa and 2 more

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.

0numbers the graph read from it
0cells of the map it votes in
90citing papers in PubMed
5.7field-weighted citation impact, top 4% 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

90 citing papers in PubMed, 138 citations in OpenAlex.

  1. Trial
  2. Quiescence to proliferation transition regulates asynchronous mitochondrial DNA replication dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Phase separation in mitochondrial fate and mitochondrial diseases.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Review
  14. Review
  15. Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. Article

30 more citing papers are in PubMed but not listed here.

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

12 authors at 7 institutions in 5 countries.

Inge KühlDepartment of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
Maria MirandaDepartment of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
Viktor PosseDepartment of Medical Biochemistry and Cell Biology, Göteborgs Universitet, 40530 Göteborg, Sweden.
Dusanka MilenkovicDepartment of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
Arnaud MourierDepartment of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.; Université de Bordeaux and the Centre National de la Recherche Scientifique, Institut de Biochimie et Génétique Cellulaires UMR 5095, Saint-Saëns, F-33077 Bordeaux, France.
Stefan J SiiraHarry Perkins Institute of Medical Research, Centre for Medical Research and School of Chemistry and Biochemistry, The University of Western Australia, Perth 6009, Australia.ORCID 0000-0002-8391-0143
Nina A BonekampDepartment of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.
Ulla NeumannCentral Microscopy, Max Planck Institute for Plant Breeding Research, 50829 Cologne, Germany.
Aleksandra FilipovskaHarry Perkins Institute of Medical Research, Centre for Medical Research and School of Chemistry and Biochemistry, The University of Western Australia, Perth 6009, Australia.
Paola Loguercio PolosaDepartment of Biosciences, Biotechnologies, and Biopharmaceutics, University of Bari Aldo Moro, 70125 Bari, Italy.
Claes M GustafssonDepartment of Medical Biochemistry and Cell Biology, Göteborgs Universitet, 40530 Göteborg, Sweden.
Nils-Göran LarssonDepartment of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany.; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177 Stockholm, Sweden.
Max Planck Institute for Biology of Ageing · DEGöteborgs Stads · SEHarry Perkins Institute of Medical Research · AUKarolinska Institutet · SEMax Planck Institute for Plant Breeding Research · DEUniversité de Bordeaux · FRUniversity of Bari Aldo Moro · IT

Funding

European Research Council 268897Medical Research Council
6 · The paper itself

Abstract

Mitochondria are vital in providing cellular energy via their oxidative phosphorylation system, which requires the coordinated expression of genes encoded by both the nuclear and mitochondrial genomes (mtDNA). Transcription of the circular mammalian mtDNA depends on a single mitochondrial RNA polymerase (POLRMT). Although the transcription initiation process is well understood, it is debated whether POLRMT also serves as the primase for the initiation of mtDNA replication. In the nucleus, the RNA polymerases needed for gene expression have no such role. Conditional knockout of Polrmt in the heart results in severe mitochondrial dysfunction causing dilated cardiomyopathy in young mice. We further studied the molecular consequences of different expression levels of POLRMT and found that POLRMT is essential for primer synthesis to initiate mtDNA replication in vivo. Furthermore, transcription initiation for primer formation has priority over gene expression. Surprisingly, mitochondrial transcription factor A (TFAM) exists in an mtDNA-free pool in the Polrmt knockout mice. TFAM levels remain unchanged despite strong mtDNA depletion, and TFAM is thus protected from degradation of the AAA(+) Lon protease in the absence of POLRMT. Last, we report that mitochondrial transcription elongation factor may compensate for a partial depletion of POLRMT in heterozygous Polrmt knockout mice, indicating a direct regulatory role of this factor in transcription. In conclusion, we present in vivo evidence that POLRMT has a key regulatory role in the replication of mammalian mtDNA and is part of a transcriptional mechanism that provides a switch between primer formation for mtDNA replication and mitochondrial gene expression.

Indexed as

Transcription, GeneticAnimalsDNA-Binding ProteinsDNA-Directed RNA PolymerasesDNA, MitochondrialDNA ReplicationGene Expression RegulationGenome, MitochondrialHigh Mobility Group ProteinsMiceDNA-Binding ProteinsDNA-Directed RNA PolymerasesDNA, MitochondrialHigh Mobility Group ProteinsPolrmt protein, mouseTfam protein, mouse7S RNAlight strand promoterMitochondriamitochondrial gene expressionmitochondrial RNA polymerasemtDNAmtDNA-free TFAM poolmtDNA replicationPOLRMT knockout mousetwinkle

Identifiers

PMID27532055
PMCPMC4975551
OpenAlexW2476107434

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.