Evidence map›Paper›PMID 22547060›Full record

ArticleThe Journal of biological chemistry2012

Pink1 kinase and its membrane potential (Deltaψ)-dependent cleavage product both localize to outer mitochondrial membrane by unique targeting mode.

Dorothea Becker, Judith Richter, Maja A Tocilescu, Serge Przedborski, Wolfgang Voos

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
4.6field-weighted citation impact, top 4% 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

47 citing papers in PubMed, 82 citations in OpenAlex.

  1. Article
  2. Article
  3. Autophagy and Mitophagy in Diabetic Kidney Disease-A Literature Review.International journal of molecular sciences · 2025
    Review
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  5. Article
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  15. Review
  16. PINK1 Content in Mitochondria is Regulated by ER-Associated Degradation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019
    Article
  17. Article
  18. 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

5 authors at 2 institutions in 2 countries.

Dorothea BeckerInstitut für Biochemie und Molekularbiologie (IBMB), Universität Bonn, Nussallee 11, 53115 Bonn, Germany.
Judith Richter
Maja A Tocilescu
Serge Przedborski
Wolfgang Voos
University of Bonn · DEColumbia University · US

Funding

TRANSLATIONAL APPROACHES TO NEUROPROTECTION OF AXONS IN PDrP50NS038370 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BURKE, ROBERT E · 1999 to 2014
$24.0M
PD iPS Cell Line Research ConsortiumRC2NS070276 · NINDS · MCLEAN HOSPITAL · PI ISACSON, OLE · 2009 to 2010
$3.8M
Proinflammatory enzymes in amytrophic lateral sclerosisR01NS042269 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI PRZEDBORSKI, SERGE E · 2001 to 2012
$3.0M
Pre-clinical testing of necrostatin as a potential small molecule for the treatmeR21NS072182 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI PRZEDBORSKI, SERGE E · 2011 to 2012
$441k
A novel cell-based high-throughput assay for ALSR21NS064191 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI PRZEDBORSKI, SERGE E · 2009 to 2010
$384k
NINDS NIH HHS NS042269NINDS NIH HHS NS064191NINDS NIH HHS NS070276NINDS NIH HHS NS072182NINDS NIH HHS NS38370NINDS NIH HHS P50 NS038370NINDS NIH HHS R01 NS042269NINDS NIH HHS R21 NS064191NINDS NIH HHS R21 NS072182NINDS NIH HHS RC2 NS070276
6 · The paper itself

Abstract

The Parkinson disease-associated kinase Pink1 is targeted to mitochondria where it is thought to regulate mitochondrial quality control by promoting the selective autophagic removal of dysfunctional mitochondria. Nevertheless, the targeting mode of Pink1 and its submitochondrial localization are still not conclusively resolved. The aim of this study was to dissect the mitochondrial import pathway of Pink1 by use of a highly sensitive in vitro assay. Mutational analysis of the Pink1 sequence revealed that its N terminus acts as a genuine matrix localization sequence that mediates the initial membrane potential (Δψ)-dependent targeting of the Pink1 precursor to the inner mitochondrial membrane, but it is dispensable for Pink1 import or processing. A hydrophobic segment downstream of the signal sequence impeded complete translocation of Pink1 across the mitochondrial inner membrane. Additionally, the C-terminal end of the protein promoted the retention of Pink1 at the outer membrane. Thus, multiple targeting signals featured by the Pink1 sequence result in the final localization of both the full-length protein and its major Δψ-dependent cleavage product to the cytosolic face of the outer mitochondrial membrane. Full-length Pink1 and deletion constructs resembling the natural Pink1 processing product were found to assemble into membrane potential-sensitive high molecular weight protein complexes at the mitochondrial surface and displayed similar cytoprotective effects when expressed in vivo, indicating that both species are functionally relevant.

Indexed as

Adenosine TriphosphateAnimalsAutophagyCations, DivalentCytosolFibroblastsGenes, RecessiveHeLa CellsHumansMembrane Potential, MitochondrialMiceMitochondrial MembranesMolecular WeightMultiprotein ComplexesParkinson DiseaseProtein KinasesAdenosine TriphosphateCations, DivalentMultiprotein ComplexesProtein KinasesPTEN-Induced Putative KinaseSulfur Isotopes

Identifiers

PMID22547060
PMCPMC3391148
OpenAlexW1968364090

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.