APD  Vol.4 No.3 , August 2015
Pink1 Rescues Gal4-Induced Developmental Defects in the Drosophila Eye
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.

Cite this paper
Todd, A. and Staveley, B. (2015) Pink1 Rescues Gal4-Induced Developmental Defects in the Drosophila Eye. Advances in Parkinson's Disease, 4, 43-48. doi: 10.4236/apd.2015.43006.
References
[1]   Weintraub, D., Comella, C.L. and Horn, S. (2008) Parkinson’s Disease—Part 1: Pathophysiology, Symptoms, Burden, Diagnosis, and Assessment. American Journal of Managed Care, 14, S40-S48.

[2]   Dawson, T.M. and Dawson, V.L. (2003) Molecular Pathways of Neurodegeneration in Parkinson’s Disease. Science, 302, 819-822. http://dx.doi.org/10.1126/science.1087753

[3]   Jendrach, M., Gispert, S., Ricciardi, F., et al. (2009) The Mitochondrial Kinase PINK1, Stress Response and Parkinson’s Disease. Journal of Bioenergetics and Biomembranes, 41, 481-486.
http://dx.doi.org/10.1007/s10863-009-9256-0

[4]   Valente, E.M., Abou-Sleiman, P.M., Caputo, V., et al. (2004) Hereditary Early-Onset Parkinson’s Disease Caused by Mutations in PINK1. Science, 304, 1158-1160.
http://dx.doi.org/10.1126/science.1096284

[5]   Valente, E.M., Salvi, S., Ialongo, T., et al. (2004) PINK1 Mutations Are Associated with Sporadic Early-Onset Parkinsonism. Annals of Neurology, 56, 336-341.
http://dx.doi.org/10.1002/ana.20256

[6]   Clark, I.E., Dodson, M.W., Jiang, C., et al. (2006) Drosophila Pink1 Is Required for Mitochondrial Function and Interacts Genetically with Parkin. Nature, 441, 1162-1166.
http://dx.doi.org/10.1038/nature04779

[7]   Exner, N., Treske, B., Paquet, D., et al. (2007) Loss-of-Function of Human PINK1 Results in Mitochondrial Pathology and Can Be Rescued by Parkin. Journal of Neuroscience, 27, 12413-12418.
http://dx.doi.org/10.1523/JNEUROSCI.0719-07.2007

[8]   Park, J., Lee, S.B., Lee, S., et al. (2006) Mitochondrial Dysfunction in Drosophila PINK1 Mutants Is Complemented by Parkin. Nature, 441, 1157-1161.
http://dx.doi.org/10.1038/nature04788

[9]   Yang, Y., Gehrke, S., Imai, Y., et al. (2006) Mitochondrial Pathology and Muscle and Dopaminergic Neuron Degeneration Caused by Inactivation of Drosophila Pink1 Is Rescued by Parkin. Proceedings of the National Academy of Sciences of the USA, 103, 10793-10798.
http://dx.doi.org/10.1073/pnas.0602493103

[10]   Hoepken, H.H., Gispert, S., Morales, B., et al. (2007) Mitochondrial Dysfunction, Peroxidation Damage and Changes in Glutathione Metabolism in PARK6. Neurobiology of Disease, 25, 401-411.
http://dx.doi.org/10.1016/j.nbd.2006.10.007

[11]   Yang, Y., Ouyang, Y., Yang, L., Beal, M.F., McQuibban, A., Vogel, H. and Lu, B. (2008) Pink1 Regulates Mitochondrial Dynamics through Interaction with the Fission/Fusion Machinery. Proceedings of the National Academy of Sciences of the United States of America, 105, 7070-7075.
http://dx.doi.org/10.1073/pnas.0711845105

[12]   Poole, A.C., Thomas, R.E., Andrews, L.A., McBride, H.M., Whitworth, A.J. and Pallanck, L.J. (2008) The PINK1/ Parkin Pathway Regulates Mitochondrial Morphology. Proceedings of the National Academy of Sciences of the United States of America, 105, 1638-1643.
http://dx.doi.org/10.1073/pnas.0709336105

[13]   Gegg, M.E., Cooper, J.M., Chau, K.Y., Rojo, M., Schapira, A.H.V. and Taanman, J.-W. (2010) Mitofusin 1 and Mitofusin 2 Are Ubiquitinated in a PINK1/Parkin-Dependent Manner upon Induction of Mitophagy. Human Molecular Genetics, 19, 4861-4870.
http://dx.doi.org/10.1093/hmg/ddq419

[14]   Vives-Bauza, C., Zhou, C., Huang, Y., Cui, M., de Vries, R.L.A., Kim, J., et al. (2010) PINK1-Dependent Recruitment of Parkin to Mitochondria in Mitophagy. Proceedings of the National Academy of Sciences of the United States of America, 107, 378-383.
http://dx.doi.org/10.1073/pnas.0911187107

[15]   Geisler, S., Holmstrom, K.M., Skujat, D., Fiesel, F.C., Rothfuss, O.C., Kahle, P.J. and Springer, W. (2010) PINK1/ Parkin-Mediated Mitophagy Is Dependent on VDAC1 and p62/SQSTM1. Nature Cell Biology, 12, 119-131. http://dx.doi.org/10.1038/ncb2012

[16]   Ziviani, E., Tao, R.N. and Whitworth, A.J. (2010) Drosophila Parkin Requires PINK1 for Mitochondrial Translocation and Ubiquitinates Mitofusin. Proceedings of the National Academy of Sciences of the United States of America, 107, 5018-5023.
http://dx.doi.org/10.1073/pnas.0913485107

[17]   Haywood, A.F. and Staveley, B.E. (2014) Parkin Counteracts Symptoms in a Drosophila Model of Parkinson’s Disease. BMC Neuroscience, 5.

[18]   Haywood, A.F. and Staveley, B.E. (2006) Mutant Alpha-Synuclein-Induced Degeneration Is Reduced by Parkin in a Fly Model of Parkinson’s Disease. Genome, 49, 505-510.
http://dx.doi.org/10.1139/G06-011

[19]   Kramer, J.M. and Staveley, B.E. (2003) GAL4 Causes Developmental Defects and Apoptosis When Expressed in the Developing Eye of Drosophila melanogaster. Genetics and Molecular Research, 2, 43-47.

[20]   Haywood, A.F.M. (2006) The Analysis of Parkin in Drosophila melanogaster. Ph.D. Dissertation, Department of Biology, Memorial University of Newfoundland, St. John’s, 157.

[21]   Todd, A.M. and Staveley, B.E. (2008) Pink1 Suppresses Alpha-Synuclein-Induced Phenotypes in a Drosophila Model of Parkinson’s Disease. Genome, 51, 1040-1046.
http://dx.doi.org/10.1139/G08-085

[22]   Yang, Y.F., Nishimura, I., Imai, Y., Takahashi, R. and Lu, B. (2003) Parkin Suppresses Dopaminergic Neuron-Selective Neurotoxicity Induced by Pael-R in Drosophila. Neuron, 37, 911-924.
http://dx.doi.org/10.1016/S0896-6273(03)00143-0

[23]   Greene, J.C., Whitworth, A.J., Kuo, I., Andrews, L.A., Feany, M.B. and Pallanck, L.J. (2003) Mitochondrial Pathology and Apoptotic Muscle Degeneration in Drosophila parkin Mutants. Proceedings of the National Academy of Sciences of the United States of America, 100, 4078-4083.
http://dx.doi.org/10.1073/pnas.0737556100

[24]   Freeman, M. (1996) Reiterative Use of the EGF Receptor Triggers Differentiation of All Cell Types in the Drosophila Eye. Cell, 87, 651-660.
http://dx.doi.org/10.1016/S0092-8674(00)81385-9

[25]   Pridgeon, J.W., Olzmann, J.A., Chin, L.S. and Li, L. (2007) PINK1 Protects against Oxidative Stress by Phosphorylating Mitochondrial Chaperone TRAP1. PLoS Biology, 5, e172.
http://dx.doi.org/10.1371/journal.pbio.0050172

 
 
Top