論文 - 詳細
| RRC ID | 88112 |
|---|---|
| 著者 | Murley A, Popovici AC, Hu XS, Lund A, Wickham K, Durieux J, Joe L, Koronyo E, Zhang H, Genuth NR, Dillin A. |
| タイトル | Quiescent cell re-entry is limited by macroautophagy-induced lysosomal damage. |
| ジャーナル | Cell |
| Abstract |
To maintain tissue homeostasis, many cells reside in a quiescent state until prompted to divide. The reactivation of quiescent cells is perturbed with aging and may underlie declining tissue homeostasis and resiliency. The unfolded protein response regulators IRE-1 and XBP-1 are required for the reactivation of quiescent cells in developmentally L1-arrested C. elegans. Utilizing a forward genetic screen in C. elegans, we discovered that macroautophagy targets protein aggregates to lysosomes in quiescent cells, leading to lysosome damage. Genetic inhibition of macroautophagy and stimulation of lysosomes via the overexpression of HLH-30 (TFEB/TFE3) synergistically reduces lysosome damage. Damaged lysosomes require IRE-1/XBP-1 for their repair following prolonged L1 arrest. Protein aggregates are also targeted to lysosomes by macroautophagy in quiescent cultured mammalian cells and are associated with lysosome damage. Thus, lysosome damage is a hallmark of quiescent cells, and limiting lysosome damage by restraining macroautophagy can stimulate their reactivation. |
| 巻・号 | 188(10) |
| ページ | 2670-2686.e14 |
| 公開日 | 2025-5-15 |
| DOI | 10.1016/j.cell.2025.03.009 |
| PII | S0092-8674(25)00282-X |
| PMID | 40203825 |
| MeSH | Animals Autophagy Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism Basic Helix-Loop-Helix Proteins Caenorhabditis elegans* / cytology Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Humans Lysosomes* / metabolism Macroautophagy* Unfolded Protein Response |
| 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 | 54 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 8.0 |
| リソース情報 | |
| 線虫 | tm2482 |