Evidence map›Paper›PMID 23259041›Full record

ArticleACS chemical neuroscience2012

Rotenone inhibits autophagic flux prior to inducing cell death.

Burton J Mader, Violetta N Pivtoraiko, Hilary M Flippo, Barbara J Klocke, Kevin A Roth, Leandra R Mangieri, John J Shacka

Open access · greenAbstract read
In one paragraph

Article in ACS chemical neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
4.7field-weighted citation impact, top 5% 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

63 citing papers in PubMed, 109 citations in OpenAlex.

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3 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

7 authors at 2 institutions in 1 country.

Burton J MaderDepartment of Pathology, Neuropathology Division, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Violetta N Pivtoraiko
Hilary M Flippo
Barbara J Klocke
Kevin A Roth
Leandra R Mangieri
John J Shacka
University of Alabama at Birmingham · USBirmingham VA Medical Center · US

Funding

Alabama Neuroscience Blueprint Core CenterP30NS057098 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI SWEATT, JOHN DAVID · 2006 to 2010
$9.5M
UAB Neuroscience Core CenterP30NS047466 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI STANDAERT, DAVID G. · 2005 to 2019
$8.5M
Molecular Characterization of Neural Stem Cell ApoptosisR01NS041962 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI ROTH, KEVIN A · 2003 to 2012
$3.0M
BCL-X DEPENDENT NEUROPATHOLOGYR01NS035107 · NINDS · WASHINGTON UNIVERSITY · PI ROTH, KEVIN A · 1996 to 2010
$2.8M
Multi-Modal Lysosomotropic Death Therapy for Malignant Peripheral Nerve Sheath TuR01CA134773 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI ROTH, KEVIN A · 2009 to 2011
$722k
NCI NIH HHS R01 CA134773NINDS NIH HHS NS047466NINDS NIH HHS NS057098NINDS NIH HHS R01 NS35107NINDS NIH HHS R01 NS41962
6 · The paper itself

Abstract

Rotenone, which selectively inhibits mitochondrial complex I, induces oxidative stress, α-synuclein accumulation, and dopaminergic neuron death, principal pathological features of Parkinson's disease. The autophagy-lysosome pathway degrades damaged proteins and organelles for the intracellular maintenance of nutrient and energy balance. While it is known that rotenone causes autophagic vacuole accumulation, the mechanism by which this effect occurs has not been thoroughly investigated. Treatment of differentiated SH-SY5Y cells with rotenone (10 μM) induced the accumulation of autophagic vacuoles at 6 h and 24 h as indicated by Western blot analysis for microtubule associated protein-light chain 3-II (MAP-LC3-II). Assessment of autophagic flux at these time points indicated that autophagic vacuole accumulation resulted from a decrease in their effective lysosomal degradation, which was substantiated by increased levels of autophagy substrates p62 and α-synuclein. Inhibition of lysosomal degradation may be explained by the observed decrease in cellular ATP levels, which in turn may have caused the observed concomitant increase in acidic vesicle pH. The early (6 h) effects of rotenone on cellular energetics and autophagy-lysosome pathway function preceded the induction of cell death and apoptosis. These findings indicate that the classical mitochondrial toxin rotenone has a pronounced effect on macroautophagy completion that may contribute to its neurotoxic potential.

Indexed as

AutophagyBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsCell DeathCell Line, TumorHumansLysosomal-Associated Membrane Protein 1LysosomesNeuronsRotenoneUncoupling AgentsVacuolesBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsLysosomal-Associated Membrane Protein 1RotenoneTFEB protein, humanUncoupling Agents

Identifiers

PMID23259041
PMCPMC3526971
OpenAlexW967958257

What OpenQuestion holds

Textmetadata
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.