PINK1 biology in neurons - logistics, contacts and protein translation

Neurons have to maintain their mitochondria locally, far from the cell body, to counter insults to this organelle. The Parkinson's disease-linked mitochondrial kinase PINK1 is central to mitochondrial quality control, and its mRNA is carried along neurons by hitch-hiking on mitochondria so that this quality sensor can be produced where it is needed.

The talk presents work showing that local translation of PINK1 depends on a concerted interplay between three organelles. Mitochondria carry the PINK1 mRNA and receive the finished protein. Downstream of insulin signalling, the RNA-anchoring complex disassembles and releases the mRNA, which relocates to the endolysosomal compartment, whose degradative function is required for PINK1 synthesis. At this contact site the endoplasmic reticulum contributes membrane-tethered chaperones that hand the newly made PINK1 precursor to mitochondria through the ER-SURF pathway.

The whole multi-organelle mechanism is needed for PINK1 to mark damaged mitochondria and target them for mitophagy in neurons.