論文 - 詳細
| RRC ID | 85192 |
|---|---|
| 著者 | Jha S, Pispa J, Holmberg CI. |
| タイトル | Impairment of proteasome-associated deubiquitinating enzyme Uchl5/UBH-4 affects autophagy. |
| ジャーナル | Biol Open |
| Abstract |
The autophagy-lysosomal pathway (ALP) and the ubiquitin-proteasome system (UPS) are the two major intracellular proteolytic systems that mediate protein turnover in eukaryotes. Although a crosstalk exists between these two systems, it is still unclear how UPS and ALP interact in vivo. Here, we investigated how impaired function of the proteasome-associated deubiquitinating enzyme (DUB) Uchl5/UBH-4 affects autophagy in human cells and in a multicellular organism. We show that downregulation of Uchl5 by siRNA reduces autophagy by partially blocking the fusion of autophagosomes with the lysosomes in HeLa cells, which is similar to a previously reported role of the proteasome-associated DUB Usp14 on autophagy. However, exposure of Caenorhabditis elegans to ubh-4 or usp-14 RNAi, or to their pharmacological inhibitors, results in diverse effects on numbers of autophagosomes and autolysosomes, without blocking the lysosomal fusion, in the intestine, hypodermal seam cells and the pharynx. Our results reveal that impairment of Uchl5/UBH-4 and Usp14 affects autophagy in a tissue context manner. A deeper insight into the interplay between UPS and ALP in various tissues in vivo has the potential to promote development of therapeutic approaches for disorders associated with proteostasis dysfunction. |
| 巻・号 | 14(2) |
| 公開日 | 2025-2-15 |
| DOI | 10.1242/bio.061644 |
| PII | 365557 |
| PMID | 39912491 |
| PMC | PMC11832120 |
| MeSH | Animals Autophagosomes / metabolism Autophagy* / genetics Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism HeLa Cells Humans Lysosomes / metabolism Proteasome Endopeptidase Complex* / metabolism Ubiquitin / metabolism Ubiquitin Thiolesterase* / genetics Ubiquitin Thiolesterase* / metabolism |
| IF | 2.029 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | Bluesky |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.2 |
| リソース情報 | |
| ヒト・動物細胞 | GFP-LC3-RFP-LC3ΔG HeLa(RCB4695) |