論文 - 詳細
| RRC ID | 11562 |
|---|---|
| 著者 | Senoo-Matsuda N, Igaki T, Miura M. |
| タイトル | Bax-like protein Drob-1 protects neurons from expanded polyglutamine-induced toxicity in Drosophila. |
| ジャーナル | EMBO J |
| Abstract |
Bcl-2 family proteins regulate cell death through the mitochondrial apoptotic pathway. Here, we show that the Drosophila Bax-like Bcl-2 family protein Drob-1 maintains mitochondrial function to protect cells from neurodegeneration. A pan-neuronal knockdown of Drob-1 results in lower locomotor activity and a shorter lifespan in adult flies. Either the RNAi-mediated downregulation of Drob-1 or overexpression of Drob-1 antagonist Buffy strongly enhances the polyglutamine-induced accumulation of ubiquitinated proteins and subsequent neurodegeneration. Furthermore, ectopic expression of Drob-1 suppresses the neurodegeneration and premature death of flies caused by expanded polyglutamine. Drob-1 knockdown decreases cellular ATP levels, and enhances respiratory inhibitor-induced mitochondrial defects such as loss of membrane potential (Deltapsim), morphological abnormalities, and reductions in activities of complex I+III and complex II+III, as well as cell death. Taken together, these results suggest that Drob-1 is essential for neuronal cell function, and that Drob-1 protects neurons from expanded polyglutamine-mediated neurodegeneration through the regulation of mitochondrial homeostasis. |
| 巻・号 | 24(14) |
| ページ | 2700-13 |
| 公開日 | 2005-7-20 |
| DOI | 10.1038/sj.emboj.7600721 |
| PII | 7600721 |
| PMID | 16001086 |
| PMC | PMC1176450 |
| MeSH | Adenosine Triphosphate / metabolism Animals Apoptosis / physiology Down-Regulation Drosophila / embryology Drosophila / genetics Drosophila / metabolism* Drosophila Proteins / genetics Drosophila Proteins / physiology* Eye Abnormalities / genetics Membrane Proteins / genetics Membrane Proteins / physiology* Mitochondria / metabolism Neurodegenerative Diseases / etiology Neurodegenerative Diseases / genetics Neurodegenerative Diseases / pathology Neurons / cytology* Neurons / metabolism* Peptides / physiology* Proto-Oncogene Proteins c-bcl-2 / genetics Proto-Oncogene Proteins c-bcl-2 / physiology bcl-2-Associated X Protein |
| IF | 9.889 |
| 引用数 | 34 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
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| 各媒体での言及数の合計 | 0 |
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