The neurotrophic factor MANF regulates autophagy and lysosome function to promote proteostasis in <i>Caenorhabditis elegans</i>.

ABSTRACT: The conserved mesencephalic astrocyte-derived neurotrophic factor (MANF) is known for protecting dopaminergic neurons and functioning in various other tissues. Previously, we showed that Caenorhabditis elegans manf-1 null mutants exhibit defects such as increased endoplasmic reticulum (ER) stress, dopaminergic neurodegeneration, and abnormal protein aggregation. These findings suggest an essential role for MANF in cellular processes. However, the mechanisms by which intracellular and extracellular MANF regulate broader cellular functions remain unclear. We report a unique mechanism of action for MANF-1 that involves the transcription factor HLH-30/TFEB-mediated signaling to regulate autophagy and lysosomal function. Multiple transgenic strains overexpressing MANF-1 showed extended l

SUBMITTER: Taylor SKB 

PROVIDER: S-EPMC11513987 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature