論文 - 詳細
| RRC ID | 69342 |
|---|---|
| 著者 | Goldsmith J, Ordureau A, Harper JW, Holzbaur ELF. |
| タイトル | Brain-derived autophagosome profiling reveals the engulfment of nucleoid-enriched mitochondrial fragments by basal autophagy in neurons. |
| ジャーナル | Neuron |
| Abstract |
Neurons depend on autophagy to maintain cellular homeostasis, and defects in autophagy are pathological hallmarks of neurodegenerative disease. To probe the role of basal autophagy in the maintenance of neuronal health, we isolated autophagic vesicles from mouse brain tissue and used proteomics to identify the major cargos engulfed within autophagosomes, validating our findings in rodent primary and human iPSC-derived neurons. Mitochondrial proteins were identified as a major cargo in the absence of mitophagy adaptors such as OPTN. We found that nucleoid-associated proteins are enriched compared with other mitochondrial components. In the axon, autophagic engulfment of nucleoid-enriched mitochondrial fragments requires the mitochondrial fission machinery Drp1. We proposed that localized Drp1-dependent fission of nucleoid-enriched fragments in proximity to the sites of autophagosome biogenesis enhances their capture. The resulting efficient autophagic turnover of nucleoids may prevent accumulation of mitochondrial DNA in the neuron, thus mitigating activation of proinflammatory pathways that contribute to neurodegeneration. |
| 巻・号 | 110(6) |
| ページ | 967-976.e8 |
| 公開日 | 2022-3-16 |
| DOI | 10.1016/j.neuron.2021.12.029 |
| PII | S0896-6273(21)01046-1 |
| PMID | 35051374 |
| PMC | PMC8930448 |
| MeSH | Animals Autophagosomes* / metabolism Autophagy / physiology Brain Mice Neurodegenerative Diseases* / metabolism Neurons / metabolism |
| IF | 14.415 |
| 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 | 148 |
| 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 | |
| 実験動物マウス | RBRC00806 |