PERK and IRE1α promote exosome secretion via blocking lysosomal degradation of multiple vesicular body.

ABSTRACT: The unfolded protein response (UPR) initiated under endoplasmic reticulum (ER) stress can not only maintain the ER homeostasis but also modulate the secretion of proteins and lipids that transmit ER stress signals among cells. Exosomes are multivesicular body (MVB)-derived extracellular vesicles, constituting the unconventional protein secretion pathway. Whether and how the secretion of exosomes is regulated by the UPR remains largely unknown. Here, we reported that ER stress induces exosome secretion in an UPR-dependent way. Activation of PERK and IRE1α, two of the UPR branches, represses the acidification and catabolic activity of lysosomes. This blocked MVB-lysosome fusion, redirecting MVBs from lysosomal degradation to plasma membrane fusion, resulting in exosome release. Calcium-media

SUBMITTER: Zhou S 

PROVIDER: S-EPMC12363578 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature