2012年10月
Function of DJ-1 in Mitochondria
YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN
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- 巻
- 132
- 号
- 10
- 開始ページ
- 1105
- 終了ページ
- 1110
- 記述言語
- 日本語
- 掲載種別
- DOI
- 10.1248/yakushi.12-00220-3
- 出版者・発行元
- PHARMACEUTICAL SOC JAPAN
Parkinson's disease is a degenerative disorder of the central nervous system caused by selective dopamine-generating cell death, and oxidative stress and mitochondrial dysfunction are thought to be responsible for the onset of Parkinson's disease. While most cases of Parkinson's disease are idiopathic, 5-10% of cases are attributed to genetic factors. DJ-1 was first identified as an activated ras-dependent oncogene and later found to be a causative gene for a familial form of Parkinson's disease, PARK7. We and others found that DJ-1 plays roles in transcriptional regulation and anti-oxidative stress function, and loss of its function is thought to affect the onset of Parkinson's disease. DJ-1 is mainly located in the cytoplasma and nucleus and partially in mitochondria. When mice or mouse cells were treated with bisphenol A, an endocrine disruptor and inducer of reactive oxygen species, DJ-1 was translocated into mitochondria to maintain mitochondrial complex 1 activity. We also found that DJ-1 directly bound to and was co-localized with NDU-FA4 and ND1, nuclear and mitochondrial DNA-encoding subunits of mitochondrial complex I, respectively, and that these associations were enhanced by oxidative stress. Furthermore, complex I activity was reduced in two types of DJ-1-knockdown NIH3T3 and HEK293 cells. These findings suggest that DJ-1 is an integral mitochondrial protein and maintains mitochondrial complex I activity to regulate mitochondrial homeostasis.
- リンク情報
- ID情報
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- DOI : 10.1248/yakushi.12-00220-3
- ISSN : 0031-6903
- PubMed ID : 23037695
- Web of Science ID : WOS:000309330300004