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

Angelika B. Harbauer; J. Tabitha Hees; Simone Wanderoy; Inmaculada Segura; Whitney Gibbs; Yiming Cheng; Martha Ordonez; Zerong Cai; Romain Cartoni; Ghazaleh Ashrafi; Chen Wang; Fabiana Perocchi; Zhigang He; Thomas L. Schwarz

doi:10.1016/j.neuron.2022.01.035

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

Angelika B. Harbauer, J. Tabitha Hees, Simone Wanderoy, Inmaculada Segura, Whitney Gibbs, Yiming Cheng, Martha Ordonez, Zerong Cai, Romain Cartoni, Ghazaleh Ashrafi, Chen Wang, Fabiana Perocchi, Zhigang He, Thomas L. Schwarz

Biology and Genomics

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Pages (from-to)	1516-1531.e9
Journal	Neuron
Volume	110
Issue number	9
DOIs	https://doi.org/10.1016/j.neuron.2022.01.035
State	Published - May 4 2022

Keywords

hitchhiking
local translation
mitophagy
OMP25
Parkinson disease
PINK1
RNA transport
synaptojanin2
SYNJ2BP

ASJC Scopus subject areas

General Neuroscience

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10.1016/j.neuron.2022.01.035

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title = "Neuronal mitochondria transport Pink1 mRNA via synaptojanin 2 to support local mitophagy",

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.",

keywords = "hitchhiking, local translation, mitophagy, OMP25, Parkinson disease, PINK1, RNA transport, synaptojanin2, SYNJ2BP",

author = "Harbauer, {Angelika B.} and Hees, {J. Tabitha} and Simone Wanderoy and Inmaculada Segura and Whitney Gibbs and Yiming Cheng and Martha Ordonez and Zerong Cai and Romain Cartoni and Ghazaleh Ashrafi and Chen Wang and Fabiana Perocchi and Zhigang He and Schwarz, {Thomas L.}",

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doi = "10.1016/j.neuron.2022.01.035",

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T1 - Neuronal mitochondria transport Pink1 mRNA via synaptojanin 2 to support local mitophagy

AU - Harbauer, Angelika B.

AU - Hees, J. Tabitha

AU - Wanderoy, Simone

AU - Segura, Inmaculada

AU - Gibbs, Whitney

AU - Cheng, Yiming

AU - Ordonez, Martha

AU - Cai, Zerong

AU - Cartoni, Romain

AU - Ashrafi, Ghazaleh

AU - Wang, Chen

AU - Perocchi, Fabiana

AU - He, Zhigang

AU - Schwarz, Thomas L.

PY - 2022/5/4

Y1 - 2022/5/4

N2 - 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.

AB - 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.

KW - hitchhiking

KW - local translation

KW - mitophagy

KW - OMP25

KW - Parkinson disease

KW - PINK1

KW - RNA transport

KW - synaptojanin2

KW - SYNJ2BP

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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