Evidence map›Paper›PMID 27889640›Full record

ArticleRedox biology2017

Inhibition of autophagy with bafilomycin and chloroquine decreases mitochondrial quality and bioenergetic function in primary neurons.

Matthew Redmann, Gloria A Benavides, Taylor F Berryhill, Willayat Y Wani, Xiaosen Ouyang, Michelle S Johnson, Saranya Ravi, Stephen Barnes, Victor M Darley-Usmar, Jianhua Zhang

Open access · goldAbstract read
In one paragraph

Article in Redox biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 159 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
159citing papers in PubMed, 1 pooled it
13.3field-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

159 citing papers in PubMed, 1 synthesis or guideline pooled it, 248 citations in OpenAlex.

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99 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

10 authors at 3 institutions in 1 country.

Matthew RedmannDepartment of Pathology and Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL 35294, United States.
Gloria A BenavidesDepartment of Pathology and Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL 35294, United States.
Taylor F BerryhillTargeted Metabolomics & Proteomics Laboratory, University of Alabama at Birmingham, Birmingham, AL 35294, United States.
Willayat Y WaniDepartment of Pathology and Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL 35294, United States.
Xiaosen OuyangDepartment of Pathology and Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL 35294, United States.
Michelle S JohnsonDepartment of Pathology and Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL 35294, United States.
Saranya RaviDepartment of Pathology and Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL 35294, United States.
Stephen BarnesTargeted Metabolomics & Proteomics Laboratory, University of Alabama at Birmingham, Birmingham, AL 35294, United States.
Victor M Darley-UsmarDepartment of Pathology and Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL 35294, United States.
Jianhua ZhangDepartment of Pathology and Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL 35294, United States; VA Medical Center, University of Alabama at Birmingham, Birmingham, AL 35294, United States. Electronic address: jianhuazhang@uabmc.edu.
University of Alabama at Birmingham · USBirmingham VA Medical Center · USTarget (United States) · US

Funding

UAB-UCSD O'Brien Core Center for Acute Kidney Injury ResearchP30DK079337 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI AGARWAL, ANUPAM · 2008 to 2022
$18.3M
Sex hormones and arthritis in a long lived animal modelP30AG050886 · NIA · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI DAVID B ALLISON · 2015 to 2026
$11.3M
Alpha-synuclein degradation mechanismsR01NS064090 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI ZHANG, JIANHUA · 2010 to 2014
$1.6M
NIA NIH HHS P30 AG050886NIDDK NIH HHS P30 DK079337NINDS NIH HHS R01 NS064090
6 · The paper itself

Abstract

Autophagy is an important cell recycling program responsible for the clearance of damaged or long-lived proteins and organelles. Pharmacological modulators of this pathway have been extensively utilized in a wide range of basic research and pre-clinical studies. Bafilomycin A1 and chloroquine are commonly used compounds that inhibit autophagy by targeting the lysosomes but through distinct mechanisms. Since it is now clear that mitochondrial quality control, particularly in neurons, is dependent on autophagy, it is important to determine whether these compounds modify cellular bioenergetics. To address this, we cultured primary rat cortical neurons from E18 embryos and used the Seahorse XF96 analyzer and a targeted metabolomics approach to measure the effects of bafilomycin A1 and chloroquine on bioenergetics and metabolism. We found that both bafilomycin and chloroquine could significantly increase the autophagosome marker LC3-II and inhibit key parameters of mitochondrial function, and increase mtDNA damage. Furthermore, we observed significant alterations in TCA cycle intermediates, particularly those downstream of citrate synthase and those linked to glutaminolysis. Taken together, these data demonstrate a significant impact of bafilomycin and chloroquine on cellular bioenergetics and metabolism consistent with decreased mitochondrial quality associated with inhibition of autophagy.

Indexed as

AnimalsAutophagyChloroquineDNA DamageDNA, MitochondrialEnergy MetabolismLysosomesMacrolidesMetabolomicsMicrotubule-Associated ProteinsMitochondriaNeuronsRatsAnxa3 protein, ratbafilomycin A1ChloroquineDNA, MitochondrialMacrolidesMicrotubule-Associated Proteins

Identifiers

PMID27889640
PMCPMC5124357
OpenAlexW2556231926

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.