UNC-49 is a redox-sensitive GABA_A receptor that regulates the mitochondrial unfolded protein response cell nonautonomously.

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 GABA_A receptor that we show is activated by hydrogen peroxide. M

SUBMITTER: Pohl F 

PROVIDER: S-EPMC10619936 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature