Identifying potential PARIS homologs in D. melanogaster.
Mitochondrial destruction leads to the formation of reactive oxygen species, increases cellular stress, causes apoptotic cell death, and involves a cascade of proteins including PARKIN, PINK1, and Mitofusin2. Mitochondrial biogenesis pathways depend upon the activity of the protein PGC-1α. These two processes are coordinated by the activity of a transcriptional repressor, Parkin interacting substrate (PARIS). The PARIS protein is degraded through the activity of the PARKIN protein, which in turn eliminates the transcriptional repression that PARIS imposes upon a downstream target, PGC-1α. Genes in this pathway have been implicated in Parkinson's disease, and there is a strong relationship between mitochondrial dysfunction and pre-mature neuron death. The identification of a PARIS homolog in Drosophila melanogaster would increase our understanding of the roles that PARIS and interacting genes play in higher organisms. We identified three potential PARIS homologs in D. melanogaster, one of which encodes a protein with similar domains to the Homo sapiens PARIS protein, CG15436. The Drosophila eye is formed from neuronal precursors, making it an ideal system to assay the effects of altered gene expression on neuronal tissue formation. The eye-specific expression of RNAi constructs for these genes revealed that both CG15269 and Crol caused neurodegenerative phenotypes, whereas CG15436 produced a phenotype similar to srl-EY. Crol-RNAi expression reduced mean lifespan when expressed in dopaminergic neurons, whereas CG15436-RNAi significantly increased lifespan. CG15436 was PARIS-like in both structure and function, and we characterized the effects of decreased gene expression in both the neuron-rich D. melanogaster eye and in dopaminergic neurons.
Department of Biology, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
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EM
Merzetti
Department of Biology, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada bestave@mun.ca.
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BE
Staveley
D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D004298:Dopamine / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D005123:Eye / Q000378:metabolism / Q000648:ultrastructure; D005786:Gene Expression Regulation; D017344:Genes, Insect; D008136:Longevity; D009410:Nerve Degeneration / Q000235:genetics; D010641:Phenotype; D034622:RNA Interference; D017386:Sequence Homology, Amino Acid; D019076:Transgenes
D029721:Drosophila Proteins; D004298:Dopamine