論文 - 詳細
| RRC ID | 57690 |
|---|---|
| 著者 | Hunt RJ, Granat L, McElroy GS, Ranganathan R, Chandel NS, Bateman JM. |
| タイトル | Mitochondrial stress causes neuronal dysfunction via an ATF4-dependent increase in L-2-hydroxyglutarate. |
| ジャーナル | J Cell Biol |
| Abstract |
Mitochondrial stress contributes to a range of neurological diseases. Mitonuclear signaling pathways triggered by mitochondrial stress remodel cellular physiology and metabolism. How these signaling mechanisms contribute to neuronal dysfunction and disease is poorly understood. We find that mitochondrial stress in neurons activates the transcription factor ATF4 as part of the endoplasmic reticulum unfolded protein response (UPR) in Drosophila We show that ATF4 activation reprograms nuclear gene expression and contributes to neuronal dysfunction. Mitochondrial stress causes an ATF4-dependent increase in the level of the metabolite L-2-hydroxyglutarate (L-2-HG) in the Drosophila brain. Reducing L-2-HG levels directly, by overexpressing L-2-HG dehydrogenase, improves neurological function. Modulation of L-2-HG levels by mitochondrial stress signaling therefore regulates neuronal function. |
| 巻・号 | 218(12) |
| ページ | 4007-4016 |
| 公開日 | 2019-12-2 |
| DOI | 10.1083/jcb.201904148 |
| PII | jcb.201904148 |
| PMID | 31645461 |
| PMC | PMC6891100 |
| MeSH | Activating Transcription Factor 4 / metabolism* Animals Brain / metabolism* Cell Nucleus / metabolism Drosophila Proteins / metabolism* Drosophila melanogaster / metabolism* Endoplasmic Reticulum / metabolism Endoplasmic Reticulum Stress Female Glutarates / metabolism* Male Mitochondria / metabolism* Mucous Membrane / metabolism Neurons / pathology* Signal Transduction Transcription Factors / metabolism* Unfolded Protein Response |
| IF | 8.811 |
| 引用数 | 3 |
| リソース情報 | |
| ショウジョウバエ | |