Evidence map›Paper›PMID 27618216›Full record

ArticleCell stem cell2016

Functional Impairment in Miro Degradation and Mitophagy Is a Shared Feature in Familial and Sporadic Parkinson's Disease.

Chung-Han Hsieh, Atossa Shaltouki, Ashley E Gonzalez, Alexandre Bettencourt da Cruz, Lena F Burbulla, Erica St Lawrence, Birgitt Schüle, Dimitri Krainc, Theo D Palmer, Xinnan Wang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell stem cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 297 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
297citing papers in PubMed, 4 pooled it
–field-weighted citation impact
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

297 citing papers in PubMed, 4 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Guideline
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  7. Mitochondrial molecular diversity in the brain.Current opinion in neurobiology · 2026
    Review
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  9. Article
  10. Article
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  12. Article
  13. The MIRO1-BAX Complex Dictates Life and Death at the Mitochondrial Gate.bioRxiv : the preprint server for biology · 2026
    Article
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237 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Chung-Han HsiehDepartment of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Atossa ShaltoukiDepartment of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Ashley E GonzalezDepartment of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Neurosciences Graduate Program, Stanford University School of Medicine, Stanford, CA 94305, USA.
Alexandre Bettencourt da CruzDepartment of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Lena F BurbullaDepartment of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Erica St LawrenceDepartment of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Birgitt SchüleParkinson's Institute and Clinical Center, Sunnyvale, CA 94085, USA.
Dimitri KraincDepartment of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Theo D PalmerDepartment of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Xinnan WangDepartment of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: xinnanw@stanford.edu.

Funding

Regulation of mitochondrial motility and mitophagy by LRRK2.R01NS089583 · NINDS · STANFORD UNIVERSITY · PI WANG, XINNAN · 2014 to 2018
$2.0M
NINDS NIH HHS R01 NS089583
6 · The paper itself

Abstract

Mitochondrial movements are tightly controlled to maintain energy homeostasis and prevent oxidative stress. Miro is an outer mitochondrial membrane protein that anchors mitochondria to microtubule motors and is removed to stop mitochondrial motility as an early step in the clearance of dysfunctional mitochondria. Here, using human induced pluripotent stem cell (iPSC)-derived neurons and other complementary models, we build on a previous connection of Parkinson's disease (PD)-linked PINK1 and Parkin to Miro by showing that a third PD-related protein, LRRK2, promotes Miro removal by forming a complex with Miro. Pathogenic LRRK2G2019S disrupts this function, delaying the arrest of damaged mitochondria and consequently slowing the initiation of mitophagy. Remarkably, partial reduction of Miro levels in LRRK2G2019S human neuron and Drosophila PD models rescues neurodegeneration. Miro degradation and mitochondrial motility are also impaired in sporadic PD patients. We reveal that prolonged retention of Miro, and the downstream consequences that ensue, may constitute a central component of PD pathogenesis.

Indexed as

MitophagyProteolysisAnimalsAxonsCell LineDopaminergic NeuronsDrosophila melanogasterHumansInduced Pluripotent Stem CellsLeucine-Rich Repeat Serine-Threonine Protein Kinase-2MitochondriaMitochondrial ProteinsMotor ActivityMutationNerve DegenerationNeuroprotectionLeucine-Rich Repeat Serine-Threonine Protein Kinase-2LRRK2 protein, humanMitochondrial Proteinsparkin proteinProtein KinasesPTEN-Induced Putative Kinaserho GTP-Binding ProteinsRHOT1 protein, humanUbiquitin-Protein Ligases

Identifiers

PMID27618216
PMCPMC5135570

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.