Cited by 159Autophagy in Disease and TherapyParkinson's Disease Mechanisms and TreatmentsMitochondrial Function and Pathology

Neuronal mitochondria transport Pink1 mRNA via synaptojanin 2 to support local mitophagy

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Harbauer, Angelika B., Hees, J. Tabitha, Wanderoy, Simone, Segura, Inmaculada, Gibbs, Whitney, Cheng, Yiming, Ordonez, Martha, Cai, Zerong +6 more·2022·Neuron

Published version of a preprint

Abstract

PTEN-induced kinase 1 (PINK1) is a short-lived protein required for the removal of damaged mitochondria through Parkin translocation and mitophagy. Because the short half-life of PINK1 limits its ability to be trafficked into neurites, local translation is required for this mitophagy pathway to be active far from the soma. The Pink1 transcript is associated and cotransported with neuronal mitochondria. In concert with translation, the mitochondrial outer membrane proteins synaptojanin 2 binding protein (SYNJ2BP) and synaptojanin 2 (SYNJ2) are required for tethering Pink1 mRNA to mitochondria via an RNA-binding domain in SYNJ2. This neuron-specific adaptation for the local translation of PINK1 provides distal mitochondria with a continuous supply of PINK1 for the activation of mitophagy.

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Authors
Harbauer, A. B., Hees, J. T., Wanderoy, S., Segura, I., Gibbs, W., Cheng, Y., Ordonez, M., Cai, Z., Cartoni, R., Ashrafi, G., Wang, C., Perocchi, F., He, Z., & Schwarz, T. L.
Affiliations
  • Boston Children's Hospital (US)
  • Max Planck Institute of Neurobiology (DE)
  • Helmholtz Munich (DE)
Corresponding author
  • Harbauer, Angelika B.
  • Schwarz, Thomas L.
Venue
Neuron
Publisher
Elsevier BV
Published
2022-05
Volume
110
Issue
9
Pages
1516-1531.e9
ISSN
0896-6273 (ISSN-L)
OpenAlex
W4225594780
Cited by
156
References
100
Citations by year
2026: 26 · 2025: 40 · 2024: 44 · 2023: 25 · 2022: 17 · 2021: 3
FWCI
23.28
Type
journal article
Language
en
Open access
Locations
  • Neuron (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion)
  • mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
  • Site cant be reached (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
  • PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
Funders
  • DFG (HA 7728/2-1)
  • Yale University (FLAG-SYNJ2a, SYNJ1-FLAG)
  • NIH (R01NS107490, P30HD018655, R01GM069808)
  • Max Planck Society
  • Jane Coffin Childs Memorial Fund for Medical Research
  • Howard Hughes Medical Institute
  • Harvard NeuroDiscovery Center (NS072030)
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords
PINK1, mitophagy, local translation, neuronal mitochondria, mitochondrial transport, RNA-binding domain, Parkin, neurites
MeSH terms
Mitochondria, Nerve Tissue Proteins, Neurons, Phosphoric Monoester Hydrolases, Protein Kinases, RNA, Messenger, Ubiquitin-Protein Ligases, Mitophagy

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