Evidence map›Paper›PMID 22428580›Full record

ArticleJournal of neurochemistry2012

Parkinson's disease-associated DJ-1 mutations impair mitochondrial dynamics and cause mitochondrial dysfunction.

Xinglong Wang, Timothy G Petrie, Yingchao Liu, Jun Liu, Hisashi Fujioka, Xiongwei Zhu

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neurochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
122citing papers in PubMed, 2 pooled it
14.0field-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

122 citing papers in PubMed, 2 syntheses or guidelines pooled it, 207 citations in OpenAlex.

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62 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

6 authors at 3 institutions in 2 countries.

Xinglong WangDepartment of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA. xiongwei.zhu@case.edu
Timothy G Petrie
Yingchao Liu
Jun Liu
Hisashi Fujioka
Xiongwei Zhu
Case Western Reserve University · USShandong University · CNShanghai Jiao Tong University · CN

Funding

LRRK2 and mitochondrial dysfunctionR21NS071184 · NINDS · CASE WESTERN RESERVE UNIVERSITY · PI ZHU, XIONGWEI · 2010 to 2011
$427k
NINDS NIH HHS R21 NS071184
6 · The paper itself

Abstract

Mitochondrial dysfunction represents a critical event during the pathogenesis of Parkinson's disease (PD) and expanding evidences demonstrate that an altered balance in mitochondrial fission/fusion is likely an important mechanism leading to mitochondrial and neuronal dysfunction/degeneration. In this study, we investigated whether DJ-1 is involved in the regulation of mitochondrial dynamics and function in neuronal cells. Confocal and electron microscopic analysis demonstrated that M17 human neuroblastoma cells over-expressing wild-type DJ-1 (WT DJ-1 cells) displayed elongated mitochondria while M17 cells over-expressing PD-associated DJ-1 mutants (R98Q, D149A and L166P) (mutant DJ-1 cells) showed significant increase of fragmented mitochondria. Similar mitochondrial fragmentation was also noted in primary hippocampal neurons over-expressing PD-associated mutant forms of DJ-1. Functional analysis revealed that over-expression of PD-associated DJ-1 mutants resulted in mitochondria dysfunction and increased neuronal vulnerability to oxidative stress (H(2) O(2)) or neurotoxin. Further immunoblot studies demonstrated that levels of dynamin-like protein (DLP1), also known as Drp1, a regulator of mitochondrial fission, was significantly decreased in WT DJ-1 cells but increased in mutant DJ-1 cells. Importantly, DLP1 knockdown in these mutant DJ-1 cells rescued the abnormal mitochondria morphology and all associated mitochondria/neuronal dysfunction. Taken together, these studies suggest that DJ-1 is involved in the regulation of mitochondrial dynamics through modulation of DLP1 expression and PD-associated DJ-1 mutations may cause PD by impairing mitochondrial dynamics and function.

Indexed as

MutationBlotting, WesternCell LineDynaminsFluorescent Antibody TechniqueGTP PhosphohydrolasesHumansIntracellular Signaling Peptides and ProteinsMicroscopy, ConfocalMicroscopy, Electron, TransmissionMicrotubule-Associated ProteinsMitochondriaMitochondrial ProteinsOncogene ProteinsParkinson DiseaseProtein Deglycase DJ-1DNM1L protein, humanDynaminsGTP PhosphohydrolasesIntracellular Signaling Peptides and ProteinsMicrotubule-Associated ProteinsMitochondrial ProteinsOncogene ProteinsPARK7 protein, humanProtein Deglycase DJ-1

Identifiers

PMID22428580
PMCPMC3740560
OpenAlexW1501828178

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.