Glutathione s-transferase omega 1 activity is sufficient to suppress neurodegeneration in a Drosophila model of Parkinson disease.
A loss-of-function mutation in the gene parkin causes a common neurodegenerative disease that may be caused by mitochondrial dysfunction. Glutathione S-transferase Omega (GSTO) is involved in cell defense mechanisms, but little is known about the role of GSTO in the progression of Parkinson disease. Here, we report that restoration of Drosophila GSTO1 (DmGSTO1), which is down-regulated in parkin mutants, alleviates some of the parkin pathogenic phenotypes and that the loss of DmGSTO1 function enhances parkin mutant phenotypes. We further identified the ATP synthase β subunit as a novel in vivo target of DmGSTO1. We found that glutathionylation of the ATP synthase β subunit is rescued by DmGSTO1 and that the expression of DmGSTO1 partially restores the activity and assembly of the mitochondrial F(1)F(0)-ATP synthase in parkin mutants. Our results suggest a novel mechanism for the protective role of DmGSTO1 in parkin mutants, through the regulation of ATP synthase activity, and provide insight into potential therapies for Parkinson disease neurodegeneration.
School of Biological Sciences, Seoul National University, Seoul 151-742, Korea.
Kiyoung
K
Kim
Song-Hee
SH
Kim
Jaekwang
J
Kim
Heuijong
H
Kim
Jeongbin
J
Yim
D000818:Animals; D004195:Disease Models, Animal; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism*; D006540:Herbicides / Q000633:toxicity; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009410:Nerve Degeneration / Q000139:chemically induced / Q000201:enzymology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010269:Paraquat / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000201:enzymology*; D010641:Phenotype; D015398:Signal Transduction / Q000502:physiology; D014404:Tubulin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D056811:Unfolded Protein Response / Q000502:physiology
D029721:Drosophila Proteins; D006540:Herbicides; D014404:Tubulin; D044767:Ubiquitin-Protein Ligases; D005982:Glutathione Transferase; D048031:JNK Mitogen-Activated Protein Kinases; D025261:Mitochondrial Proton-Translocating ATPases; C487430:park protein, Drosophila; D010269:Paraquat