論文 - 詳細
| RRC ID | 15565 |
|---|---|
| 著者 | Kanda H, Igaki T, Okano H, Miura M. |
| タイトル | Conserved metabolic energy production pathways govern Eiger/TNF-induced nonapoptotic cell death. |
| ジャーナル | Proc Natl Acad Sci U S A |
| Abstract |
Caspase-independent cell death is known to be important in physiological and pathological conditions, but its molecular regulation is not well-understood. Eiger is the sole fly ortholog of TNF. The ectopic expression of Eiger in the developing eye primordium caused JNK-dependent but caspase-independent cell death. To understand the molecular basis of this Eiger-induced nonapoptotic cell death, we performed a large-scale genetic screen in Drosophila for suppressors of the Eiger-induced cell death phenotype. We found that molecules that regulate metabolic energy production are central to this form of cell death: it was dramatically suppressed by decreased levels of molecules that regulate cytosolic glycolysis, mitochondrial β-oxidation of fatty acids, the tricarboxylic acid cycle, and the electron transport chain. Importantly, reducing the expression of energy production-related genes did not affect the cell death triggered by proapoptotic genes, such as reaper, hid, or debcl, indicating that the energy production-related genes have a specific role in Eiger-induced nonapoptotic cell death. We also found that energy production-related genes regulate the Eiger-induced cell death downstream of JNK. In addition, Eiger induced the production of reactive oxygen species in a manner dependent on energy production-related genes. Furthermore, we showed that this cell death machinery is involved in Eiger's physiological function, because decreasing the energy production-related genes suppressed Eiger-dependent tumor suppression, an intrinsic mechanism for removing tumorigenic mutant clones from epithelia by inducing cell death. This result suggests a link between sensitivity to cell death and metabolic activity in cancer. |
| 巻・号 | 108(47) |
| ページ | 18977-82 |
| 公開日 | 2011-11-22 |
| DOI | 10.1073/pnas.1103242108 |
| PII | 1103242108 |
| PMID | 22065747 |
| PMC | PMC3223446 |
| MeSH | Adenosine Triphosphate / metabolism Animals Animals, Genetically Modified Cell Death / physiology* Drosophila / embryology* Drosophila Proteins / metabolism Drosophila Proteins / physiology* Energy Metabolism / genetics Energy Metabolism / physiology* Eye / embryology* Eye / metabolism Gene Expression Regulation, Developmental / physiology* Genotype Immunohistochemistry Membrane Proteins / metabolism Membrane Proteins / physiology* RNA Interference Reactive Oxygen Species / metabolism Tumor Necrosis Factor-alpha / metabolism* |
| IF | 9.412 |
| 引用数 | 33 |
| WOS 分野 | 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 | F1000Research |
| 各媒体での言及数の合計 | 1 |
| 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 | |
| ショウジョウバエ | 5516R-1 7486R-2 |