Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-47871
Saini, N; Georgiev, O; Schaffner, W (2011). Parkin mutant in the fly is largely rescued by metal-responsive transcription factor (MTF-1). Molecular and Cellular Biology, 31(10):2151-2161.
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The gene for Parkin, an E3 ubiquitin ligase, is mutated in some familial forms of Parkinson's disease, a severe neurodegenerative disorder. A homozygous mutant of the Drosophila ortholog of human parkin is viable but results in severe motoric impairment including an inability to fly, female and male sterility, and a decreased lifespan. Here we show that a double mutant of the genes for Parkin and the metal-responsive transcription factor MTF-1 is not viable. MTF-1, which is conserved from insects to mammals, is a key regulator of heavy metal homeostasis and detoxification and plays additional roles in other stress conditions, notably oxidative stress. In contrast to the synthetic lethality of the double mutant, elevated expression of MTF-1 dramatically ameliorates the parkin mutant phenotype, as evidenced by prolonged lifespan, motoric improvement including short flight episodes, and female fertility. At the cellular level, muscle and mitochondrial structures are substantially improved. A beneficial effect is also seen with a transgene encoding human MTF-1. We propose that Parkin and MTF-1 provide complementary functions in metal homeostasis, oxidative stress and other cellular stress responses.
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|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||07 Faculty of Science > Institute of Molecular Life Sciences|
|DDC:||570 Life sciences; biology|
|Uncontrolled Keywords:||Drosophila/ MTF-1/ metal homeostasis/ parkin/ Parkinson’s disease|
|Deposited On:||07 Apr 2011 07:46|
|Last Modified:||27 Nov 2013 20:15|
|Publisher:||American Society for Microbiology|
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