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

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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, Cartoni, Romain, Ashrafi, Ghazaleh, Wang, Chen, Perocchi, Fabiana, He, Zhigang, Schwarz, Thomas L.·2022·Neuron

DOI 10.1016/j.neuron.2022.01.035PMC PMC9081165

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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.
ORCID: Harbauer, Angelika B.
Hees, J. Tabitha
Wanderoy, Simone
Segura, Inmaculada
Cheng, Yiming
Cai, Zerong
Cartoni, Romain
Ashrafi, Ghazaleh
Wang, Chen
Perocchi, Fabiana
He, Zhigang
Schwarz, Thomas L.
Venue: Neuron
Publisher: Elsevier BV
Published: 2022-05
Volume: 110
Issue: 9
Pages: 1516-1531.e9
ISSN: 0896-6273 (ISSN-L)
DOI: 10.1016/j.neuron.2022.01.035
PMC: PMC9081165
OpenAlex: W4225594780
Cited by: 156
References: 100
Citations by year: 2026: 26 · 2025: 40 · 2024: 44 · 2023: 25 · 2022: 17
FWCI: 23.28
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 368 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
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: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Health Sciences › Medicine › Clinical 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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Neuronal mitochondria transport Pink1 mRNA via synaptojanin 2 to support local mitophagy

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