Evidence map›Paper›PMID 30417335›Full record

ArticleJournal of cellular physiology2019

MicroRNA-382 silencing induces a mitonuclear protein imbalance and activates the mitochondrial unfolded protein response in muscle cells.

Dennis Dahlmans, Alexandre Houzelle, Pénélope Andreux, Xu Wang, Johanna A Jörgensen, Norman Moullan, Sabine Daemen, Sander Kersten, Johan Auwerx, Joris Hoeks

Open access · hybridAbstract read
In one paragraph

Article in Journal of cellular physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
0.9field-weighted citation impact, top 25% 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

19 citing papers in PubMed, 21 citations in OpenAlex.

  1. Review
  2. Article
  3. Chaperonin in health and disease.Molecular biomedicine · 2026
    Review
  4. Review
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Mitochondrial cross-compartmental signalling to maintain proteostasis and longevity.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2020
    Review
  16. Mitonuclear genomics and aging.Human genetics · 2020
    Review
  17. Article
  18. Review
  19. Article
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

10 authors at 3 institutions in 2 countries.

Dennis DahlmansDepartment of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, The Netherlands.
Alexandre HouzelleDepartment of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, The Netherlands.
Pénélope AndreuxLaboratory of Integrative Systems Physiology, Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Xu WangLaboratory of Integrative Systems Physiology, Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Johanna A JörgensenDepartment of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, The Netherlands.
Norman MoullanLaboratory of Integrative Systems Physiology, Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Sabine DaemenDepartment of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, The Netherlands.
Sander KerstenDivision of Human Nutrition, Nutrition, Metabolism and Genomics Group, Wageningen University, Wageningen, The Netherlands.
Johan AuwerxLaboratory of Integrative Systems Physiology, Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Joris HoeksDepartment of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, The Netherlands.ORCID 0000-0002-0265-0870
Maastricht University · NLÉcole Polytechnique Fédérale de Lausanne · CHWageningen University & Research · NL

Funding

Translational Systems Genetics of Mitochondria, Metabolism, and AgingR01AG043930 · NIA · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI WILLIAMS, ROBERT W. · 2013 to 2017
$2.5M
NIA NIH HHS R01 AG043930
6 · The paper itself

Abstract

Proper mitochondrial function plays a central role in cellular metabolism. Various diseases as well as aging are associated with diminished mitochondrial function. Previously, we identified 19 miRNAs putatively involved in the regulation of mitochondrial metabolism in skeletal muscle, a highly metabolically active tissue. In the current study, these 19 miRNAs were individually silenced in C2C12 myotubes using antisense oligonucleotides, followed by measurement of the expression of 27 genes known to play a major role in regulating mitochondrial metabolism. Based on the outcomes, we then focused on miR-382-5p and identified pathways affected by its silencing using microarrays, investigated protein expression, and studied cellular respiration. Silencing of miRNA-382-5p significantly increased the expression of several genes involved in mitochondrial dynamics and biogenesis. Conventional microarray analysis in C2C12 myotubes silenced for miRNA-382-5p revealed a collective downregulation of mitochondrial ribosomal proteins and respiratory chain proteins. This effect was accompanied by an imbalance between mitochondrial proteins encoded by the nuclear and mitochondrial DNA (1.35-fold, p < 0.01) and an induction of HSP60 protein (1.31-fold, p < 0.05), indicating activation of the mitochondrial unfolded protein response (mtUPR). Furthermore, silencing of miR-382-5p reduced basal oxygen consumption rate by 14% ( p < 0.05) without affecting mitochondrial content, pointing towards a more efficient mitochondrial function as a result of improved mitochondrial quality control. Taken together, silencing of miR-382-5p induces a mitonuclear protein imbalance and activates the mtUPR in skeletal muscle, a phenomenon that was previously associated with improved longevity.

Indexed as

AnimalsMiceMicroRNAsMitochondriaMitochondrial ProteinsMitochondria, MuscleMuscle Fibers, SkeletalMuscle, SkeletalRibosomal ProteinsUnfolded Protein ResponseMicroRNAsMIRN382 microRNA, humanMitochondrial ProteinsRibosomal ProteinsmicroRNAmitochondriaprotein stressskeletal muscle

Identifiers

PMID30417335
PMCPMC6344277
OpenAlexW2900687678

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.