論文 - 詳細
| RRC ID | 21879 |
|---|---|
| 著者 | Kim K, Kim SH, Kim J, Kim H, Yim J. |
| タイトル | Glutathione s-transferase omega 1 activity is sufficient to suppress neurodegeneration in a Drosophila model of Parkinson disease. |
| ジャーナル | J Biol Chem |
| Abstract |
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. |
| 巻・号 | 287(9) |
| ページ | 6628-41 |
| 公開日 | 2012-2-24 |
| DOI | 10.1074/jbc.M111.291179 |
| PII | S0021-9258(20)61147-4 |
| PMID | 22219196 |
| PMC | PMC3307323 |
| MeSH | Animals Disease Models, Animal Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster Glutathione Transferase / genetics Glutathione Transferase / metabolism* Herbicides / toxicity JNK Mitogen-Activated Protein Kinases / metabolism Male Mitochondrial Proton-Translocating ATPases / metabolism Mutagenesis, Site-Directed Nerve Degeneration / chemically induced Nerve Degeneration / enzymology* Oxidative Stress / drug effects Oxidative Stress / physiology Paraquat / toxicity Parkinsonian Disorders / enzymology* Phenotype Signal Transduction / physiology Tubulin / metabolism Ubiquitin-Protein Ligases / genetics* Unfolded Protein Response / physiology |
| IF | 4.238 |
| 引用数 | 25 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| リソース情報 | |
| ショウジョウバエ | 11154R-1 11154R-3 |