Evidence map›Paper›PMID 26377859›Full record

ArticleCirculation. Cardiovascular genetics2015

Translational Regulation of the Mitochondrial Genome Following Redistribution of Mitochondrial MicroRNA in the Diabetic Heart.

Rajaganapathi Jagannathan, Dharendra Thapa, Cody E Nichols, Danielle L Shepherd, Janelle C Stricker, Tara L Croston, Walter A Baseler, Sara E Lewis, Ivan Martinez, John M Hollander

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

Article in Circulation. Cardiovascular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed, 2 pooled it
3.5field-weighted citation impact, top 7% 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

78 citing papers in PubMed, 2 syntheses or guidelines pooled it, 118 citations in OpenAlex.

  1. Noncoding RNA as potential therapeutics to rescue mitochondrial dysfunction in cardiovascular diseases.American journal of physiology. Heart and circulatory physiology · 2025
    Pooled it
  2. Pooled it
  3. A Distinct Population of Mitochondrial miRNA in Human Male Skeletal Muscle Assessed Before and After Exercise.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  4. Article
  5. Review
  6. Article
  7. The roles of subcellular Argonaute 2 in cardiovascular diseases.Journal of translational internal medicine · 2025
    Article
  8. Skeletal Muscle Mitochondria Contain Nuclear-Encoded RNA Species Prior to and Following Adaptation to Exercise Training in Rats.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  9. Review
  10. Article
  11. Purification of mitochondria from skeletal muscle tissue for transcriptomic analyses reveals localization of nuclear-encoded noncoding RNAs.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Article
  12. Article
  13. Guidelines for mitochondrial RNA analysis.Molecular therapy. Nucleic acids · 2024
    Review
  14. Article
  15. Acute endoplasmic reticulum stress-induced mitochondria respiratory chain damage: The role of activated calpains.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 2 countries.

Rajaganapathi JagannathanFrom the Department of Human Performances, Division of Exercise Physiology (R.J., D.T., C.E.N., D.L.S., J.C.S., T.L.C., W.A.B., S.E.L., J.M.H.), Center for Cardiovascular and Respiratory Sciences (R.J., D.T., C.E.N., D.L.S., T.L.C., W.A.B., S.E.L., J.M.H.), Department of Microbiology, Immunology and Cell Biology (I.M.), and Mary Babb Randolph Cancer Center (I.M.), West Virginia University School of Medicine, Morgantown.
Dharendra ThapaFrom the Department of Human Performances, Division of Exercise Physiology (R.J., D.T., C.E.N., D.L.S., J.C.S., T.L.C., W.A.B., S.E.L., J.M.H.), Center for Cardiovascular and Respiratory Sciences (R.J., D.T., C.E.N., D.L.S., T.L.C., W.A.B., S.E.L., J.M.H.), Department of Microbiology, Immunology and Cell Biology (I.M.), and Mary Babb Randolph Cancer Center (I.M.), West Virginia University School of Medicine, Morgantown.
Cody E NicholsFrom the Department of Human Performances, Division of Exercise Physiology (R.J., D.T., C.E.N., D.L.S., J.C.S., T.L.C., W.A.B., S.E.L., J.M.H.), Center for Cardiovascular and Respiratory Sciences (R.J., D.T., C.E.N., D.L.S., T.L.C., W.A.B., S.E.L., J.M.H.), Department of Microbiology, Immunology and Cell Biology (I.M.), and Mary Babb Randolph Cancer Center (I.M.), West Virginia University School of Medicine, Morgantown.
Danielle L ShepherdFrom the Department of Human Performances, Division of Exercise Physiology (R.J., D.T., C.E.N., D.L.S., J.C.S., T.L.C., W.A.B., S.E.L., J.M.H.), Center for Cardiovascular and Respiratory Sciences (R.J., D.T., C.E.N., D.L.S., T.L.C., W.A.B., S.E.L., J.M.H.), Department of Microbiology, Immunology and Cell Biology (I.M.), and Mary Babb Randolph Cancer Center (I.M.), West Virginia University School of Medicine, Morgantown.
Janelle C StrickerFrom the Department of Human Performances, Division of Exercise Physiology (R.J., D.T., C.E.N., D.L.S., J.C.S., T.L.C., W.A.B., S.E.L., J.M.H.), Center for Cardiovascular and Respiratory Sciences (R.J., D.T., C.E.N., D.L.S., T.L.C., W.A.B., S.E.L., J.M.H.), Department of Microbiology, Immunology and Cell Biology (I.M.), and Mary Babb Randolph Cancer Center (I.M.), West Virginia University School of Medicine, Morgantown.
Tara L CrostonFrom the Department of Human Performances, Division of Exercise Physiology (R.J., D.T., C.E.N., D.L.S., J.C.S., T.L.C., W.A.B., S.E.L., J.M.H.), Center for Cardiovascular and Respiratory Sciences (R.J., D.T., C.E.N., D.L.S., T.L.C., W.A.B., S.E.L., J.M.H.), Department of Microbiology, Immunology and Cell Biology (I.M.), and Mary Babb Randolph Cancer Center (I.M.), West Virginia University School of Medicine, Morgantown.
Walter A BaselerFrom the Department of Human Performances, Division of Exercise Physiology (R.J., D.T., C.E.N., D.L.S., J.C.S., T.L.C., W.A.B., S.E.L., J.M.H.), Center for Cardiovascular and Respiratory Sciences (R.J., D.T., C.E.N., D.L.S., T.L.C., W.A.B., S.E.L., J.M.H.), Department of Microbiology, Immunology and Cell Biology (I.M.), and Mary Babb Randolph Cancer Center (I.M.), West Virginia University School of Medicine, Morgantown.
Sara E LewisFrom the Department of Human Performances, Division of Exercise Physiology (R.J., D.T., C.E.N., D.L.S., J.C.S., T.L.C., W.A.B., S.E.L., J.M.H.), Center for Cardiovascular and Respiratory Sciences (R.J., D.T., C.E.N., D.L.S., T.L.C., W.A.B., S.E.L., J.M.H.), Department of Microbiology, Immunology and Cell Biology (I.M.), and Mary Babb Randolph Cancer Center (I.M.), West Virginia University School of Medicine, Morgantown.
Ivan MartinezFrom the Department of Human Performances, Division of Exercise Physiology (R.J., D.T., C.E.N., D.L.S., J.C.S., T.L.C., W.A.B., S.E.L., J.M.H.), Center for Cardiovascular and Respiratory Sciences (R.J., D.T., C.E.N., D.L.S., T.L.C., W.A.B., S.E.L., J.M.H.), Department of Microbiology, Immunology and Cell Biology (I.M.), and Mary Babb Randolph Cancer Center (I.M.), West Virginia University School of Medicine, Morgantown.
John M HollanderFrom the Department of Human Performances, Division of Exercise Physiology (R.J., D.T., C.E.N., D.L.S., J.C.S., T.L.C., W.A.B., S.E.L., J.M.H.), Center for Cardiovascular and Respiratory Sciences (R.J., D.T., C.E.N., D.L.S., T.L.C., W.A.B., S.E.L., J.M.H.), Department of Microbiology, Immunology and Cell Biology (I.M.), and Mary Babb Randolph Cancer Center (I.M.), West Virginia University School of Medicine, Morgantown. jhollander@hsc.wvu.edu.
Anna Needs Neuroblastoma Answers · USJagannath University · IN

Funding

West Virginia IDEA-CTRU54GM104942 · NIGMS · WEST VIRGINIA UNIVERSITY · PI GARY O RANKIN · 2012 to 2026
$81.0M
WV INBRE: The Inhibitor of Growth Family Member 4 (ING4) inhibits L-Type Amino Acid Transporter 1 (LAT1) expression to suppress Breast CancerP20GM103434 · NIGMS · MARSHALL UNIVERSITY · PI Trupti Joshi · 2012 to 2026
$61.1M
COBRE Transitional Center in NeuroscienceP30GM103503 · NIGMS · WEST VIRGINIA UNIVERSITY · PI SPIROU, GEORGE A · 2012 to 2014
$3.2M
Mechanisms of Diabetic Cardiomyopathy: Mitochondria Subpopulations Brought to FocDP2DK083095 · NIDDK · WEST VIRGINIA UNIVERSITY · PI HOLLANDER, JOHN M · 2008 to 2010
$2.3M
Research Training in Cardiovascular and Pulmonary DiseasesT32HL090610 · NHLBI · WEST VIRGINIA UNIVERSITY · PI MUSTAFA, S. JAMAL · 2008 to 2012
$1.5M
NHLBI NIH HHS T32 HL090610NHLBI NIH HHS T32HL090610NIDDK NIH HHS DP2 DK083095NIDDK NIH HHS DP2DK083095NIGMS NIH HHS 8P20GM10343412NIGMS NIH HHS GM103503NIGMS NIH HHS P20 GM103434NIGMS NIH HHS P30 GM103503NIGMS NIH HHS U54 GM104942NIGMS NIH HHS U54GM104942
6 · The paper itself

Abstract

backgroundCardiomyocytes are rich in mitochondria which are situated in spatially distinct subcellular regions, including those under the plasma membrane, subsarcolemmal mitochondria, and those between the myofibrils, interfibrillar mitochondria. We previously observed subpopulation-specific differences in mitochondrial proteomes following diabetic insult. The objective of this study was to determine whether mitochondrial genome-encoded proteins are regulated by microRNAs inside the mitochondrion and whether subcellular spatial location or diabetes mellitus influences the dynamics. METHODS AND

resultsUsing microarray technology coupled with cross-linking immunoprecipitation and next generation sequencing, we identified a pool of mitochondrial microRNAs, termed mitomiRs, that are redistributed in spatially distinct mitochondrial subpopulations in an inverse manner following diabetic insult. Redistributed mitomiRs displayed distinct interactions with the mitochondrial genome requiring specific stoichiometric associations with RNA-induced silencing complex constituents argonaute-2 (Ago2) and fragile X mental retardation-related protein 1 (FXR1) for translational regulation. In the presence of Ago2 and FXR1, redistribution of mitomiR-378 to the interfibrillar mitochondria following diabetic insult led to downregulation of mitochondrially encoded F0 component ATP6. Next generation sequencing analyses identified specific transcriptome and mitomiR sequences associated with ATP6 regulation. Overexpression of mitomiR-378 in HL-1 cells resulted in its accumulation in the mitochondrion and downregulation of functional ATP6 protein, whereas antagomir blockade restored functional ATP6 protein and cardiac pump function.

conclusionsWe propose mitomiRs can translationally regulate mitochondrially encoded proteins in spatially distinct mitochondrial subpopulations during diabetes mellitus. The results reveal the requirement of RNA-induced silencing complex constituents in the mitochondrion for functional mitomiR translational regulation and provide a connecting link between diabetic insult and ATP synthase function.

Indexed as

Genome, MitochondrialProtein BiosynthesisAnimalsDiabetes Mellitus, ExperimentalDiabetic CardiomyopathiesMiceMicroRNAsMitochondria, HeartMitochondrial ProteinsRNARNA, MitochondrialMicroRNAsMitochondrial ProteinsRNARNA, Mitochondrialcardiacdiabetes mellitusgenomemicroRNAsmitochondriamitochondrialmyocytes

Identifiers

PMID26377859
PMCPMC4681669
OpenAlexW2204902737

What OpenQuestion holds

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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.