Neurotrophic factor MANF regulates autophagy and lysosome function to promote proteostasis in C. elegans.

ABSTRACT: The conserved mesencephalic astrocyte-derived neurotrophic factor (MANF) protects dopaminergic neurons but also functions in several other tissues. Previously, we showed that Caenorhabditis elegans manf-1 null mutants have increased ER stress, dopaminergic neurodegeneration, protein aggregation, slower growth, and a reduced lifespan. The multiple requirements of MANF in different systems suggest its essential role in regulating cellular processes. However, how intracellular and extracellular MANF regulates broader cellular function remains unknown. Here, we report a novel mechanism of action for manf-1 that involves the autophagy transcription factor HLH-30/TFEB-mediated signaling to regulate lysosomal function and aging. We generated multiple transgenic strains overexpressin

SUBMITTER: Taylor SKB 

PROVIDER: S-EPMC10802257 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature