Good news!
"Scientists have finally pinned down a protein that’s largely responsible for Parkinson’s disease. Known as PINK1, the protein has been linked to the disease for decades but its structure and how to switch it back on have remained elusive – until now. ...
“This is the first time we’ve seen human PINK1 docked to the surface of damaged mitochondria and it has uncovered a remarkable array of proteins that act as the docking site,” ..."
"... PINK1 works in four distinct steps, with the first two steps not been seen before.
First, PINK1 senses mitochondrial damage. Then it attaches to damaged mitochondria. Once attached it tags ubiquitin, which then links to a protein called Parkin so that the damaged mitochondria can be recycled. ..."
From the abstract:
"Mutations in the ubiquitin kinase PINK1 cause early onset Parkinson’s Disease, but how PINK1 is stabilized at depolarized mitochondrial translocase complexes has remained poorly understood.
We determined a 3.1-Å resolution cryo-electron microscopy structure of dimeric human PINK1 stabilized at an endogenous array of mitochondrial TOM and VDAC complexes. Symmetric arrangement of two TOM core complexes around a central VDAC2 dimer is facilitated by TOM5 and TOM20, both of which also bind PINK1 kinase C-lobes. PINK1 enters mitochondria through the proximal TOM40 barrel of the TOM core complex, guided by TOM7 and TOM22.
Our structure explains how human PINK1 is stabilized at the TOM complex and regulated by oxidation, uncovers a previously unknown TOM-VDAC assembly, and reveals how a physiological substrate traverses TOM40 during translocation."
Scientists solve decades-long Parkinson’s mystery (original news release)
Structure of human PINK1 at a mitochondrial TOM-VDAC array (no public access)
A model of two PINK1 proteins attached to the mitochondria membrane
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