Evidence map›Paper›PMID 25730670›Full record

ArticleNature neuroscience2015

Mitochondrial control by DRP1 in brain tumor initiating cells.

Qi Xie, Qiulian Wu, Craig M Horbinski, William A Flavahan, Kailin Yang, Wenchao Zhou, Stephen M Dombrowski, Zhi Huang, Xiaoguang Fang, Yu Shi and 4 more

Open access · greenAbstract read
In one paragraph

Article in Nature neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 263 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
263citing papers in PubMed, 1 pooled it
15.7field-weighted citation impact, top 1% 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

263 citing papers in PubMed, 1 synthesis or guideline pooled it, 416 citations in OpenAlex.

  1. Pooled it
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  15. Article
  16. Review
  17. Conformational Rearrangement of Fission DSPs.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
  18. Article
  19. Metabolic adaptations of brain metastasis.Nature reviews. Cancer · 2025
    Review
  20. Article

203 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

14 authors at 5 institutions in 3 countries.

Qi XieDepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland, Ohio, USA.
Qiulian WuDepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland, Ohio, USA.
Craig M HorbinskiDepartment of Pathology, University of Kentucky, Lexington, Kentucky, USA.
William A FlavahanDepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland, Ohio, USA.
Kailin Yang1] Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland, Ohio, USA. [2] Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA.ORCID 0000000159686738
Wenchao ZhouDepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland, Ohio, USA.
Stephen M DombrowskiDepartment of Neurological Surgery, Cleveland Clinic, Cleveland, Ohio, USA.
Zhi HuangDepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland, Ohio, USA.
Xiaoguang FangDepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland, Ohio, USA.
Yu ShiDepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland, Ohio, USA.
Ashley N FergusonDepartment of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, Virginia, USA.
David F KashatusDepartment of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, Virginia, USA.
Shideng Bao1] Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland, Ohio, USA. [2] Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA.
Jeremy N Rich1] Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland, Ohio, USA. [2] Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA.
Institute for Stem Cell Biology and Regenerative Medicine · INCleveland Clinic Lerner College of Medicine · USUniversity of Virginia · USCleveland Clinic · USUniversity of Kentucky · US

Funding

University of Kentucky Markey Cancer Center Support Grant ECIA SupplementP30CA177558 · NCI · UNIVERSITY OF KENTUCKY · PI Jennifer F Rogers · 2013 to 2026
$38.3M
UNDERSTANDING THE MOLECULAR BASIS OF EPIGENETIC TRANSCRIPTIONAL SILENCINGP20RR020171 · NCRR · UNIVERSITY OF KENTUCKY · PI WATT, DAVID · 2004 to 2011
$16.5M
Targeting Ferritin in GlioblastomaR01CA169117 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI BAO, SHIDENG, CONNOR, JAMES ROBERT · 2013 to 2017
$2.7M
Metabolism Informs Intertumoral & Intratumoral HeterogeneityR01NS087913 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI NAKANO, ICHIRO, RICH, JEREMY N · 2014 to 2018
$2.0M
Targeting Brain Tumor Stem Cells Through Novel Therapeutic CombinationsR01CA154130 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI RICH, JEREMY N · 2010 to 2014
$1.9M
Molecular Targeting of L1CAM to Inhibit Glioblastoma Stem Cell InvasionR01NS070315 · NINDS · CLEVELAND CLINIC LERNER COM-CWRU · PI BAO, SHIDENG · 2010 to 2014
$1.7M
Energy Stress in Brain Tumor Initiating Stem CellsR01NS089272 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI RICH, JEREMY N · 2014 to 2018
$1.7M
The Significance of Isocitrate Dehydrogenase Mutations in GliomasK08CA155764 · NCI · UNIVERSITY OF KENTUCKY · PI HORBINSKI, CRAIG MICHAEL · 2011 to 2015
$857k
Instructive Cues in Glioblastoma HierarchiesR01CA171652 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI RICH, JEREMY N · 2014 to 2014
$421k
NCI NIH HHS CA154130NCI NIH HHS CA155764NCI NIH HHS CA169117NCI NIH HHS CA171652NCI NIH HHS K08 CA155764NCI NIH HHS P30 CA177558NCI NIH HHS P30CA177558NCI NIH HHS R01 CA154130NCI NIH HHS R01 CA169117NCI NIH HHS R01 CA171652NCRR NIH HHS 2P20 RR020171NCRR NIH HHS P20 RR020171NINDS NIH HHS NS070315NINDS NIH HHS NS087913NINDS NIH HHS NS089272NINDS NIH HHS R01 NS070315NINDS NIH HHS R01 NS087913NINDS NIH HHS R01 NS089272
6 · The paper itself

Abstract

Brain tumor initiating cells (BTICs) co-opt the neuronal high affinity glucose transporter, GLUT3, to withstand metabolic stress. We investigated another mechanism critical to brain metabolism, mitochondrial morphology, in BTICs. BTIC mitochondria were fragmented relative to non-BTIC tumor cell mitochondria, suggesting that BTICs increase mitochondrial fission. The essential mediator of mitochondrial fission, dynamin-related protein 1 (DRP1), showed activating phosphorylation in BTICs and inhibitory phosphorylation in non-BTIC tumor cells. Targeting DRP1 using RNA interference or pharmacologic inhibition induced BTIC apoptosis and inhibited tumor growth. Downstream, DRP1 activity regulated the essential metabolic stress sensor, AMP-activated protein kinase (AMPK), and targeting AMPK rescued the effects of DRP1 disruption. Cyclin-dependent kinase 5 (CDK5) phosphorylated DRP1 to increase its activity in BTICs, whereas Ca(2+)-calmodulin-dependent protein kinase 2 (CAMK2) inhibited DRP1 in non-BTIC tumor cells, suggesting that tumor cell differentiation induces a regulatory switch in mitochondrial morphology. DRP1 activation correlated with poor prognosis in glioblastoma, suggesting that mitochondrial dynamics may represent a therapeutic target for BTICs.

Indexed as

ApoptosisBrain NeoplasmsCell Line, TumorDynaminsGlioblastomaGTP PhosphohydrolasesHumansMicrotubule-Associated ProteinsMitochondriaMitochondrial ProteinsNeoplastic Stem CellsPhosphorylationPrognosisDNM1L protein, humanDynaminsGTP PhosphohydrolasesMicrotubule-Associated ProteinsMitochondrial Proteins

Identifiers

PMID25730670
PMCPMC4376639
OpenAlexW2074617654

What OpenQuestion holds

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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.