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bioRxiv · 10.1101/2024.06.21.600039

ER-associated biogenesis of PINK1 preprotein for neuronal mitophagy

Hees, J. T.·Segura, I.·Schneider, A.·Schifferer, M.·Misgeld, T.·Harbauer, A. B.
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Abstract

A central role in mitochondrial quality control is played by the Parkinson-related mitochondrial kinase PINK1, whose mRNA is transported in neurons by mitochondrial hitch- hiking. Using a live-cell imaging assay for the translation of the PINK1 precursor, we show that local translation of PINK1 requires a concerted interplay between mitochondria and the ER in neurons. For efficient translation, the Pink1 mRNA needs to relocate to ribosomes located near endolysosomes and the ER. The ER membrane-tethered chaperone DNAJB6 then shields the PINK1 precursor on transit to mitochondria following the ER-SURF pathway. Loss of DNAJB6 hence leads to persistence of ER/endolysosome-associated PINK1 precursor stores and failure of mitophagy upon mitochondrial damage.

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Hees, J. T., Segura, I., Schneider, A., Schifferer, M., Misgeld, T., Harbauer, A. B.. 2024-06-24. ER-associated biogenesis of PINK1 preprotein for neuronal mitophagy. https://doi.org/10.1101/2024.06.21.600039

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