| RRC ID |
80958
|
| 著者 |
Pohl F, Germann AL, Mao J, Hou S, Bakare B, Kong Thoo Lin P, Yates K, Nonet ML, Akk G, Kornfeld K, Held JM.
|
| タイトル |
UNC-49 is a redox-sensitive GABAA receptor that regulates the mitochondrial unfolded protein response cell nonautonomously.
|
| ジャーナル |
Sci Adv
|
| Abstract |
The γ-aminobutyric acid-mediated (GABAergic) system participates in many aspects of organismal physiology and disease, including proteostasis, neuronal dysfunction, and life-span extension. Many of these phenotypes are also regulated by reactive oxygen species (ROS), but the redox mechanisms linking the GABAergic system to these phenotypes are not well defined. Here, we report that GABAergic redox signaling cell nonautonomously activates many stress response pathways in Caenorhabditis elegans and enhances vulnerability to proteostasis disease in the absence of oxidative stress. Cell nonautonomous redox activation of the mitochondrial unfolded protein response (mitoUPR) proteostasis network requires UNC-49, a GABAA receptor that we show is activated by hydrogen peroxide. MitoUPR induction by a spinocerebellar ataxia type 3 (SCA3) C. elegans neurodegenerative disease model was similarly dependent on UNC-49 in C. elegans. These results demonstrate a multi-tissue paradigm for redox signaling in the GABAergic system that is transduced via a GABAA receptor to function in cell nonautonomous regulation of health, proteostasis, and disease.
|
| 巻・号 |
9(44)
|
| ページ |
eadh2584
|
| 公開日 |
2023-11-3
|
| DOI |
10.1126/sciadv.adh2584
|
| PMID |
37910615
|
| PMC |
PMC10619936
|
| MeSH |
Animals
Caenorhabditis elegans / metabolism
Caenorhabditis elegans Proteins* / genetics
Caenorhabditis elegans Proteins* / metabolism
Neurodegenerative Diseases*
Oxidation-Reduction
Receptors, GABA-A / metabolism
Unfolded Protein Response
|
| リソース情報 |
| 線虫 |
tm5487 |
