論文 - 詳細
| RRC ID | 45852 |
|---|---|
| 著者 | Segref A, Kevei É, Pokrzywa W, Schmeisser K, Mansfeld J, Livnat-Levanon N, Ensenauer R, Glickman MH, Ristow M, Hoppe T. |
| タイトル | Pathogenesis of human mitochondrial diseases is modulated by reduced activity of the ubiquitin/proteasome system. |
| ジャーナル | Cell Metab |
| Abstract |
Mitochondria maintain cellular homeostasis by coordinating ATP synthesis with metabolic activity, redox signaling, and apoptosis. Excessive levels of mitochondria-derived reactive oxygen species (ROS) promote mitochondrial dysfunction, triggering numerous metabolic disorders. However, the molecular basis for the harmful effects of excessive ROS formation is largely unknown. Here, we identify a link between mitochondrial stress and ubiquitin-dependent proteolysis, which supports cellular surveillance both in Caenorhabditis elegans and humans. Worms defective in respiration with elevated ROS levels are limited in turnover of a GFP-based substrate protein, demonstrating that mitochondrial stress affects the ubiquitin/proteasome system (UPS). Intriguingly, we observed similar proteolytic defects for disease-causing IVD and COX1 mutations associated with mitochondrial failure in humans. Together, these results identify a conserved link between mitochondrial metabolism and ubiquitin-dependent proteostasis. Reduced UPS activity during pathological conditions might potentiate disease progression and thus provides a valuable target for therapeutic intervention. |
| 巻・号 | 19(4) |
| ページ | 642-52 |
| 公開日 | 2014-4-1 |
| DOI | 10.1016/j.cmet.2014.01.016 |
| PII | S1550-4131(14)00022-9 |
| PMID | 24703696 |
| MeSH | Adenosine Triphosphate / metabolism Animals Animals, Genetically Modified Caenorhabditis elegans Cell Line Cyclooxygenase 1 / genetics Electrophoresis, Polyacrylamide Gel Green Fluorescent Proteins Humans Immunoblotting Mitochondrial Diseases / metabolism* Mitochondrial Diseases / physiopathology Mutagenesis Organic Chemicals Oxidative Phosphorylation Proteasome Endopeptidase Complex / metabolism* Proteolysis Reactive Oxygen Species / metabolism* Ubiquitin / metabolism* Ubiquitin-Protein Ligases / metabolism |
| IF | 21.567 |
| 引用数 | 60 |
| WOS 分野 | ENDOCRINOLOGY & METABOLISM CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm2371 tm544 tm4853 |