Evidence map›Paper›PMID 25588501›Full record

ArticleeLife2015

Mitochondrial Ca(2+) uptake by the voltage-dependent anion channel 2 regulates cardiac rhythmicity.

Hirohito Shimizu, Johann Schredelseker, Jie Huang, Kui Lu, Shamim Naghdi, Fei Lu, Sarah Franklin, Hannah Dg Fiji, Kevin Wang, Huanqi Zhu and 13 more

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

Article in eLife, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
2.9field-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

54 citing papers in PubMed, 86 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Zebrafish in Cardiovascular Disease Research: from Model to Application.International journal of biological sciences · 2026
    Review
  5. Review
  6. Synthesis through C(spAccounts of chemical research · 2025
    Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. STING Suppresses Mitochondrial VDAC2 to Govern RCC Growth Independent of Innate Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Article
  13. Review
  14. Inositol 1,4,5-trisphosphate receptors in cardiomyocyte physiology and disease.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2022
    Review
  15. Functional remodelling of perinuclear mitochondria alters nucleoplasmic CaPhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2022
    Article
  16. Review
  17. Review
  18. Review
  19. Review
  20. 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

23 authors at 4 institutions in 3 countries.

Hirohito ShimizuDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States.
Johann SchredelsekerDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States.
Jie HuangDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States.
Kui LuDepartment of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, United States.
Shamim NaghdiMitoCare Center, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, United States.
Fei LuDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States.
Sarah FranklinDepartment of Anesthesiology, University of California, Los Angeles, Los Angeles, United States.
Hannah Dg FijiDepartment of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, United States.
Kevin WangDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States.
Huanqi ZhuDepartment of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, United States.
Cheng TianDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States.
Billy LinDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States.
Haruko NakanoDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States.
Amy EhrlichMitoCare Center, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, United States.
Junichi NakaiBrain Science Institute, Saitama University, Saitama, Japan.
Adam Z StiegCalifornia NanoSystems Institute, University of California, Los Angeles, Los Angeles, United States.
James K GimzewskiDepartment of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, United States.
Atsushi NakanoDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States.
Joshua I GoldhaberCedars-Sinai Heart Institute, Los Angeles, United States.
Thomas M VondriskaDepartment of Anesthesiology, University of California, Los Angeles, Los Angeles, United States.
György HajnóczkyMitoCare Center, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, United States.
Ohyun KwonDepartment of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, United States.
Jau-Nian ChenDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States.
University of California, Los Angeles · USThomas Jefferson University · USCalifornia NanoSystems Institute · USSaitama University · JP

Funding

Phosphine-Catalyzed Annulations and Their ApplicationsR01GM071779 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI OHYUN KWON · 2006 to 2026
$5.7M
Dynamics of Cardiac Nuclei in Heart DiseaseR01HL105699 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI VONDRISKA, THOMAS M. · 2011 to 2025
$5.0M
Molecular Biology of Cardiac Sodium-Calcium ExchangeR01HL048509 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GOLDHABER, JOSHUA I, PHILIPSON, KENNETH · 2002 to 2016
$4.7M
MITOCHONDRIAL CALCIUM SIGNALING IN CELL DEATHR01GM059419 · NIGMS · THOMAS JEFFERSON UNIVERSITY · PI HAJNOCZKY, GYORGY · 2000 to 2016
$4.0M
Metabolic Regulation of Cardiac E-C CouplingR01HL070828 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GOLDHABER, JOSHUA I · 2002 to 2013
$3.8M
Patterning of the Primitive Heart Tube in ZebrafishR01HL081700 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHEN, JAU-NIAN · 2007 to 2010
$1.5M
Elucidating the molecular mechanisms regulating embryonic cardiac rhythmicityR01HL096980 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHEN, JAU-NIAN · 2010 to 2013
$1.5M
Pilot-Scale Library Production Based on Phosphine Catalysis of AllenesP41GM081282 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KWON, OHYUN · 2007 to 2009
$1.4M
Reprogramming of cardiac genome by Smyd1 in hypertrophy and failureR00HL107674 · NHLBI · UNIVERSITY OF UTAH · PI FRANKLIN, SARAH · 2012 to 2014
$691k
The role of electromechanical cue on cardiomyocyte maturationR21HL124503 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GIMZEWSKI, JAMES K, NAKANO, ATSUSHI · 2015 to 2016
$407k
Calcium Signaling, Metabolism, and EC Coupling in HeartR56HL070828 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GOLDHABER, JOSHUA I · 2008 to 2008
$385k
Reprogramming of cardiac genome by Smyd1 in hypertrophy and failureK99HL107674 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FRANKLIN, SARAH · 2011 to 2012
$206k
NHLBI NIH HHS HL070828NHLBI NIH HHS HL081700NHLBI NIH HHS HL096980NHLBI NIH HHS HL105699NHLBI NIH HHS HL107674NHLBI NIH HHS K99 HL107674NHLBI NIH HHS R00 HL107674NHLBI NIH HHS R01 HL048509NHLBI NIH HHS R01 HL070828NHLBI NIH HHS R01 HL081700NHLBI NIH HHS R01 HL096980NHLBI NIH HHS R01 HL105699NHLBI NIH HHS R21 HL124503NHLBI NIH HHS R56 HL070828NIGMS NIH HHS GM059419NIGMS NIH HHS GM071779NIGMS NIH HHS P41 GM081282NIGMS NIH HHS P41GM081282NIGMS NIH HHS R01 GM059419NIGMS NIH HHS R01 GM071779
6 · The paper itself

Abstract

Tightly regulated Ca(2+) homeostasis is a prerequisite for proper cardiac function. To dissect the regulatory network of cardiac Ca(2+) handling, we performed a chemical suppressor screen on zebrafish tremblor embryos, which suffer from Ca(2+) extrusion defects. Efsevin was identified based on its potent activity to restore coordinated contractions in tremblor. We show that efsevin binds to VDAC2, potentiates mitochondrial Ca(2+) uptake and accelerates the transfer of Ca(2+) from intracellular stores into mitochondria. In cardiomyocytes, efsevin restricts the temporal and spatial boundaries of Ca(2+) sparks and thereby inhibits Ca(2+) overload-induced erratic Ca(2+) waves and irregular contractions. We further show that overexpression of VDAC2 recapitulates the suppressive effect of efsevin on tremblor embryos whereas VDAC2 deficiency attenuates efsevin's rescue effect and that VDAC2 functions synergistically with MCU to suppress cardiac fibrillation in tremblor. Together, these findings demonstrate a critical modulatory role for VDAC2-dependent mitochondrial Ca(2+) uptake in the regulation of cardiac rhythmicity.

Indexed as

Heart RateAmino Acid SequenceAnimalsCalciumCalcium SignalingEmbryo, MammalianHeartMitochondriaMolecular Sequence DataMyocardial ContractionMyocytes, CardiacVideo RecordingVoltage-Dependent Anion Channel 2ZebrafishZebrafish ProteinsCalciumVoltage-Dependent Anion Channel 2Zebrafish Proteinsarrhythmiacalcium handlingcell biologydevelopmental biologyfibrillationhearthumanmitochondriamousestem cellsVDACzebrafish

Identifiers

PMID25588501
PMCPMC4293673
OpenAlexW2135014000

What OpenQuestion holds

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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.