Reference - Detail
| RRC ID | 87622 |
|---|---|
| Author | Shinno K, Miura Y, Iijima KM, Suzuki E, Ando K. |
| Title | Axonal distribution of mitochondria maintains neuronal autophagy during aging via eIF2β. |
| Journal | Elife |
| Abstract |
Neuronal aging and neurodegenerative diseases are accompanied by proteostasis collapse, while the cellular factors that trigger it have not been identified. Impaired mitochondrial transport in the axon is another feature of aging and neurodegenerative diseases. Using Drosophila, we found that genetic depletion of axonal mitochondria causes dysregulation of protein degradation. Axons with mitochondrial depletion showed abnormal protein accumulation and autophagic defects. Lowering neuronal ATP levels by blocking glycolysis did not reduce autophagy, suggesting that autophagic defects are associated with mitochondrial distribution. We found that eIF2β was increased by the depletion of axonal mitochondria via proteome analysis. Phosphorylation of eIF2α, another subunit of eIF2, was lowered, and global translation was suppressed. Neuronal overexpression of eIF2β phenocopied the autophagic defects and neuronal dysfunctions, and lowering eIF2β expression rescued those perturbations caused by depletion of axonal mitochondria. These results indicate the mitochondria-eIF2β axis maintains proteostasis in the axon, of which disruption may underlie the onset and progression of age-related neurodegenerative diseases. |
| Volume | 13 |
| Published | 2026-1-26 |
| DOI | 10.7554/eLife.95576 |
| PII | 95576 |
| PMID | 41587080 |
| PMC | PMC12834499 |
| MeSH | Aging* Animals Autophagy* Axons* / metabolism Axons* / physiology Drosophila Proteins* / genetics Drosophila Proteins* / metabolism Drosophila melanogaster* / physiology Eukaryotic Initiation Factor-2* / metabolism Eukaryotic Initiation Factor-2B* / genetics Eukaryotic Initiation Factor-2B* / metabolism Mitochondria* / metabolism Neurons* / metabolism Neurons* / physiology Proteostasis |
| IF | 7.08 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 16 |
| Altmetric score changes over past 6months | 2.1 |
| Resource | |
| Drosophila | DGRC#142114 |