Evidence map›Paper›PMID 26512955›Full record

ArticleCell death & disease2015

A conserved MADS-box phosphorylation motif regulates differentiation and mitochondrial function in skeletal, cardiac, and smooth muscle cells.

W Mughal, L Nguyen, S Pustylnik, S C da Silva Rosa, S Piotrowski, D Chapman, M Du, N S Alli, J Grigull, A J Halayko and 10 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

33 citing papers in PubMed, 59 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. FoxP1 Represses MEF2A in Striated Muscle.Molecular and cellular biology · 2024
    Article
  12. Review
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Review
  19. Mitophagy in Diabetic Cardiomyopathy: Roles and Mechanisms.Frontiers in cell and developmental biology · 2021
    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

20 authors at 6 institutions in 2 countries.

W MughalDepartment of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB, Canada.
L NguyenThe Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Theme of the Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB, Canada.
S PustylnikDepartment of Biology, York University, Toronto, ON, Canada.
S C da Silva RosaDepartment of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB, Canada.
S PiotrowskiDepartment of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB, Canada.
D ChapmanThe Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Theme of the Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB, Canada.
M DuDepartment of Biology, York University, Toronto, ON, Canada.
N S AlliDepartment of Biology, York University, Toronto, ON, Canada.
J GrigullDepartment of Biology, York University, Toronto, ON, Canada.
A J HalaykoDepartment of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB, Canada.
M AlianiDepartment of Human Nutritional Sciences, University of Manitoba, Winnipeg, MB, Canada.
M K TophamHuntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
R M EpandDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
G M HatchThe Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Theme of the Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB, Canada.
T J PereiraThe Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Theme of the Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB, Canada.
S KereliukThe Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Theme of the Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB, Canada.
J C McDermottDepartment of Biology, York University, Toronto, ON, Canada.
C RampitschAgriculture and Agrifood Canada, Morden, MB, Canada.
V W DolinskyThe Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Theme of the Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB, Canada.
J W GordonDepartment of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB, Canada.
University of Manitoba · CAYork University · CAChildren's Hospital Research Institute of Manitoba · CAAgriculture and Agri-Food Canada · CAHuntsman Cancer Institute · USMcMaster University · CA

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

Exposure to metabolic disease during fetal development alters cellular differentiation and perturbs metabolic homeostasis, but the underlying molecular regulators of this phenomenon in muscle cells are not completely understood. To address this, we undertook a computational approach to identify cooperating partners of the myocyte enhancer factor-2 (MEF2) family of transcription factors, known regulators of muscle differentiation and metabolic function. We demonstrate that MEF2 and the serum response factor (SRF) collaboratively regulate the expression of numerous muscle-specific genes, including microRNA-133a (miR-133a). Using tandem mass spectrometry techniques, we identify a conserved phosphorylation motif within the MEF2 and SRF Mcm1 Agamous Deficiens SRF (MADS)-box that regulates miR-133a expression and mitochondrial function in response to a lipotoxic signal. Furthermore, reconstitution of MEF2 function by expression of a neutralizing mutation in this identified phosphorylation motif restores miR-133a expression and mitochondrial membrane potential during lipotoxicity. Mechanistically, we demonstrate that miR-133a regulates mitochondrial function through translational inhibition of a mitophagy and cell death modulating protein, called Nix. Finally, we show that rodents exposed to gestational diabetes during fetal development display muscle diacylglycerol accumulation, concurrent with insulin resistance, reduced miR-133a, and elevated Nix expression, as young adult rats. Given the diverse roles of miR-133a and Nix in regulating mitochondrial function, and proliferation in certain cancers, dysregulation of this genetic pathway may have broad implications involving insulin resistance, cardiovascular disease, and cancer biology.

Indexed as

Amino Acid MotifsAnimalsCell DifferentiationCells, CulturedChlorocebus aethiopsCOS CellsDiabetes, GestationalFemaleGene Expression RegulationHumansMEF2 Transcription FactorsMembrane Potential, MitochondrialMicroRNAsMitochondriaMuscle Fibers, SkeletalMutagenesis, Site-DirectedMEF2 Transcription FactorsMicroRNAsMIRN133 microRNA, humanSerum Response Factor

Identifiers

PMID26512955
PMCPMC5399178
OpenAlexW2258479317

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.