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PINK1 Protein Crucial for Removing Damaged Mitochondria


Cells are powered by tiny energy reactors called mitochondria. When damaged, they leak destructive molecules that can cause substantial harm and eventually kill brain cells. According to an article published in Nature (12 August 2015), it was shown that a protein called PINK1, that is implicated in Parkinson’s disease, is critical for helping cells get rid of dysfunctional mitochondria. According to the new research, PINK1 does this by triggering an intricate process called mitophagy that breaks down and removes damaged mitochondria from the cell.


Mutations in PINK1 and its partner molecule Parkin cause hereditary forms of Parkinson’s disease (PD). Moreover, the inability to remove defective mitochondria from nerve cells has been linked to numerous neurodegenerative diseases, including the more common forms of PD and amyotrophic lateral sclerosis (ALS). It was previously considered that Parkin was essential to destroy damaged mitochondria, but the new research discovered that PINK1 can initiate this process without Parkin.


Study results showed that PINK1 recruits two proteins called Optineurin and NDP52 to the surface of mitochondria. These proteins, in turn, recruit a variety of other protein molecules that mark the mitochondria for degradation. Optineurin and NDP52 are members of a group of proteins called autophagy receptors. When cells were created that contained no autophagy receptors, it was found that the cells could not dispose of malfunctioning mitochondria. However, when the function of either Optineurin or NDP52 was restored, the cells regained this ability. Reinstating other autophagy receptors had little or no effect.


According to the authors, knowing that Optineurin and NDP52 are the primary autophagy receptors involved in this process can inform about the cause of different human diseases. For example, Optineurin is mutated in ALS and also in certain forms of glaucoma, whereas NDP52 is known to be mutated in Crohn’s disease. This suggests that problems with mitophagy may be involved in those diseases.


When PINK1 accumulates on the surface of defective mitochondria, it alters a molecule called ubiquitin. The modified ubiquitin then recruits autophagy receptors as well as Parkin. Parkin promotes mitophagy by bringing more ubiquitin to the mitochondria to form long chains that flag damaged mitochondria for removal. Since PINK1 is needed to start building these ubiquitin chains, the current observations suggest a new avenue for creating drugs that treat disease by boosting the disposal of damaged mitochondria.


A number of companies are trying to develop drugs to activate this pathway and some are trying to find drugs that activate Parkin. However, this new model might suggest a different strategy where it may not be so important to activate Parkin, but more important to activate PINK1.”



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