The cause of Parkinsons?

One of the more frustrating things about being a scientist is we often spend weeks, even months, between discovering (or reading about discoveries) that make a real impact in fields we're interested in. The last week was far from a frustrating week, in fact large advances were made in two areas I'm interested in (plus a bunch of cool stuff in other area's, like figuring out the colouration of some dinosaurs). Weeks like this are rare, so I'm dedicating the next two posts simply to what happened last week.

This post is on an amazing discovery in regards to Parkinsons disease, a degenerative neurological disease that affects many of the elderly. Parkinsons itself has been known to be partially a defect in mitochondria - the energy-generating parts of our cells. For reasons that are still a mystery, the buildup of broken mitochondria leads to neurodegenerative diseases like Parkinsons. We've known for a long time that Parkinsons is partially genetic, and a few genes have been identified as culprits. Two in particular have been known to be major players and - PINK1 and Parkin. But while these two genes have been known to be important for a while, exactly what they did to cause Parkinsons disease was unknown - until last week.



As it turns out these two genes play a role in regulating the removal of damaged mitochondria. PINK1 has been known to be stuck to mitochondria, where it is though to phosphorylate proteins on mitochondria that are no longer functioning properly. For those of you who are not bio majors, phosphoryaltion simply attaches a little chemical tag to a protein. That tag can be recognised by other proteins, or can modify the activity of the tagged protein itself. Exactly what that tag did, in terms of getting rid of damaged mitochondria, has long been a mystery.

As it turns out the purpose of that tag is to bring in another protein, called Parkin, to the mitochondria. As odd as it may seem, Parkin's job is to attach another kind of tag onto proteins - a tag called "ubiquitin" (picture to right). On the surface tagging a tag may seem a little redundant, at least it does until you realise that ubiquitin is a very special kind of tag - ubiquitin is usually used by our cells to tag things for destruction. So PARK1 and Parkin act as a team; PARK1 sits on mitochondria and acts as a sensor. When PARK1 detects that a mitochondria is not functioning properly it phosphorylates (tags) the mitochondria. This tag brings in Parkin which then adds the final tag that leads to the destruction of the defective mitochondria, through a process called autophagy (literally "self-eating).

You'd think that figuring out how these proteins work would be enough to make a scientist happy - but no, this group had to take things a little further. Not only did they discover how these two genes act to destroy defective mitochondria (and thus prevent Parkinsons), but they also showed that the mutations in these genes most often found in people with Parkinsons prevent this process from occurring.

What is really exciting is what this potentially offers for patients. At the very least this discovery may lead to genetic tests that would allow us to detect potential Parkinsons patients decades before they become symptomatic - perhaps allowing us to treat the disease before it happens. But it also opens up the door to other options - new drug regimens, gene therapies, even stem cell therapies, to treat - or even better - prevent Parkinsons.


Geisler S, Holmström KM, Skujat D, Fiesel FC, Rothfuss OC, Kahle PJ, & Springer W (2010). PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nature cell biology, 12 (2), 119-31 PMID: 20098416