Neuronal mitochondria transport Pink1 mRNA via synaptojanin 2 to support local mitophagy
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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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PINK1 is a target of T cell responses in Parkinson’s disease
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Axonal mitophagy in retinal ganglion cells
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Emerging implications for ribosomes in proximity to mitochondria
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Mitochondrial dynamics reveal potential to facilitate axonal regeneration after spinal cord injury
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LncRNA Tug1 Regulates Post-Stroke Microglial Pyroptosis via PINK1/Parkin-Mediated Mitophagy
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Self-citationEndoplasmic reticulum – condensate interactions in protein synthesis and secretion
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A human-specific microRNA controls the timing of excitatory synaptogenesis
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Enhancing CNS mitophagy: drug development and disease-relevant models
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Autophagy at the synapse, an early site of dysfunction in neurodegeneration
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Mitochondrial hitch-hiking of Pink1 mRNA supports axonal mitophagy
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Self-citationNeuronal compartmentalization results in “impoverished” axonal mitochondriaPreprint
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Self-citationMitochondrial specialization and signaling shape neuronal function
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Proteome Dynamics in iPSC-Derived Human Dopaminergic Neurons
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PINK1 is a target of T cell responses in Parkinson’s diseasePreprint
Williams, G. P., Michaelis, T., Lima-Júnior, J. R., Frazier, A., Tran, N. K., Phillips, E. J., Mallal, S. A., Litvan, I., Goldman, J. G., Alcalay, R. N., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.02.09.579465 · Cited by 8 · see citing works
Presynapses are mitophagy pit stops that prevent axon degenerationPreprint
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Mitophagy: A key regulator in the pathophysiology and treatment of spinal cord injury
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Regulation of Subcellular Protein Synthesis for Restoring Neural Connectivity
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Preparation of Viable Human Neurites for Neurobiological and Neurodegeneration Studies
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Self-citationGUCY2C signaling limits dopaminergic neuron vulnerability to toxic insults
Cheslow, L., Byrne, M. D., Kopenhaver, J. S., Iacovitti, L., Smeyne, R. J., Snook, A. E., & Waldman, S. A. (2024) · npj Parkinson s Disease · doi:10.1038/s41531-024-00697-z · Cited by 7 · see citing works
ER-associated biogenesis of PINK1 preprotein for neuronal mitophagyPreprint
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Molecular mechanisms of PINK1/Parkin-mediated mitochondrial quality control
Bayne, A. N., & Trempe, J. (2026) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2026.02.014 · Cited by 5 · see citing works
The role of mitochondrial mRNA translation in cellular communication
Zilio, E., Schlegel, T., Zaninello, M., & Rugarli, E. I. (2025) · Journal of Cell Science · doi:10.1242/jcs.263753 · Cited by 5 · see citing works
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A long-lived pool of PINK1 imparts a molecular memory of depolarization-induced activity
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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
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2022-05
- Volume
- 110
- Issue
- 9
- Pages
- 1516-1531.e9
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC9081165
- 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
- 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
- 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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