Evidence map›Paper›PMID 29287112›Full record

ArticlePloS one2017

Mitochondrial DNA depletion by ethidium bromide decreases neuronal mitochondrial creatine kinase: Implications for striatal energy metabolism.

Emily Booth Warren, Aidan Edward Aicher, Joshua Patrick Fessel, Christine Konradi

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
0.6field-weighted citation impact, top 32% 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

20 citing papers in PubMed, 33 citations in OpenAlex.

  1. Article
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  6. Review
  7. A roadmap for ribosome assembly in human mitochondria.Nature structural & molecular biology · 2024
    Article
  8. Article
  9. Mitochondrial DNA is a key driver in cigarette smoke extract-induced IL-6 expression.Hypertension research : official journal of the Japanese Society of Hypertension · 2024
    Article
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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

4 authors at 1 institution in 1 country.

Emily Booth WarrenDepartment of Pharmacology, Vanderbilt University, Nashville, Tennessee, United States of America.
Aidan Edward AicherDepartment of Biological Sciences, Vanderbilt University, Nashville, Tennessee, United States of America.
Joshua Patrick FesselDepartment of Pharmacology, Vanderbilt University, Nashville, Tennessee, United States of America.
Christine KonradiDepartment of Pharmacology, Vanderbilt University, Nashville, Tennessee, United States of America.ORCID 0000-0003-3494-714X
Vanderbilt University · US

Funding

Levodopa dyskinesia and striatal neuroplasticityR01NS048235 · NINDS · VANDERBILT UNIVERSITY · PI KONRADI, CHRISTINE L · 2004 to 2007
$1.3M
Metabolic Reprogramming in Pulmonary Arterial HypertensionK08HL121174 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI FESSEL, JOSHUA PATRICK · 2014 to 2018
$723k
Console upgrades for biological NMR spectrometersS10RR025677 · NCRR · VANDERBILT UNIVERSITY · PI SANDERS, CHARLES R · 2009 to 2009
$460k
XFe96 AnalyzerS10OD018015 · OD · VANDERBILT UNIVERSITY · PI LANNIGAN, DEBORAH · 2014 to 2014
$200k
NCRR NIH HHS S10 RR025677NHLBI NIH HHS K08 HL121174NIH HHS 1S10OD018015NIH HHS S10 OD018015NIH HHS S10 RR025677NINDS NIH HHS R01 NS048235
6 · The paper itself

Abstract

Mitochondrial DNA (mtDNA), the discrete genome which encodes subunits of the mitochondrial respiratory chain, is present at highly variable copy numbers across cell types. Though severe mtDNA depletion dramatically reduces mitochondrial function, the impact of tissue-specific mtDNA reduction remains debated. Previously, our lab identified reduced mtDNA quantity in the putamen of Parkinson's Disease (PD) patients who had developed L-DOPA Induced Dyskinesia (LID), compared to PD patients who had not developed LID and healthy subjects. Here, we present the consequences of mtDNA depletion by ethidium bromide (EtBr) treatment on the bioenergetic function of primary cultured neurons, astrocytes and neuron-enriched cocultures from rat striatum. We report that EtBr inhibition of mtDNA replication and transcription consistently reduces mitochondrial oxygen consumption, and that neurons are significantly more sensitive to EtBr than astrocytes. EtBr also increases glycolytic activity in astrocytes, whereas in neurons it reduces the expression of mitochondrial creatine kinase mRNA and levels of phosphocreatine. Further, we show that mitochondrial creatine kinase mRNA is similarly downregulated in dyskinetic PD patients, compared to both non-dyskinetic PD patients and healthy subjects. Our data support a hypothesis that reduced striatal mtDNA contributes to energetic dysregulation in the dyskinetic striatum by destabilizing the energy buffering system of the phosphocreatine/creatine shuttle.

Indexed as

Energy MetabolismAnimalsCells, CulturedCorpus StriatumCreatine KinaseDNA, MitochondrialEthidiumGlycolysisHumansMitochondriaOxygen ConsumptionRatsRats, Sprague-DawleyCreatine KinaseDNA, MitochondrialEthidium

Identifiers

PMID29287112
PMCPMC5747477
OpenAlexW2779920959

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.