Abstract
Parkinson disease pathology often includes the presence of ubiquitin-positive, α-synuclein-enriched inclusions in the remaining neurons. Pink1 (also identified as PARK6) encodes a serinethreonine kinase involved in mitochondrial protection that works with parkin to ubiquitinate various proteins, promoting mitophagy. The parkin protein works to tag cystolic proteins for degradation, and previous work in our laboratory has shown the ability of parkin to rescue a Gal4-induced phenotype. To further investigate the role of Pink1 in protection against toxic proteins, we have performed expression studies to determine the effects of increases and decreases in Pink1 on the Gal4-induced phenotype consisting of developmental defects in the Drosophila eye. Our results show that Pink1 is able to rescue the Gal4-induced phenotype, highlighting a protective role for Pink1 against toxic proteins. When expressing low levels of Gal4, reductions in Pink1 or parkin are not able to induce a phenotype. This suggests that Pink1 or parkin may counter Gal4 effects despite reductions, or that the effects of low level Gal4 may be alleviated by an alternative mechanism. Moreover, the Pink1 mechanism of action during differing types of cell stress, including degradation of toxic proteins, warrants further investigation.
Highlights
Parkinson disease (PD) is the most prevalent neurodegenerative movement disorder [1]
Co-overexpression with two copies of the Pink1 transgene results in a further, significant reduction of the Gal4-induced phenotype, near control levels (0.5% disruption, 95% CI). These results suggest that an increase in Pink1, in a dose dependent manner, during eye development is able to alleviate the detrimental effects of Gal4 expression
The ability of Pink1 to counteract the effects of GMR-Gal4 is similar to previous results in our laboratory with parkin [20], supporting the theory that Pink1 is acting via parkin
Summary
Parkinson disease (PD) is the most prevalent neurodegenerative movement disorder [1]. Pink is involved in mitochondrial protection, as loss of function of Pink results in substantial mitochondrial defects in sensitive tissues [6]-[10]. The recruitment of parkin to the mitochondria by Pink results in the ubiquitination of various mitochondrial proteins, promoting mitophagy [13][16]. Pink may have a protective role apart from the mitochondria, where an interaction with parkin could result in the tagging of cystolic proteins for degradation. This may be an important, but largely overlooked role, as neurodegenerative diseases are often characterized by the accumulation of toxic proteins
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