Language

English

Publication Date

8-26-2025

Journal

Cell Reports

DOI

10.1016/j.celrep.2025.116070

PMID

40742812

PMCID

PMC12478994

PubMedCentral® Posted Date

9-30-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Injury causes differentiated cells to undergo massive reprogramming to become proliferative and repair tissue via paligenosis. Gastric chief cells use paligenosis to reprogram into progenitor-like spasmolytic-polypeptide-expressing metaplasia (SPEM) cells. Stage 1 of paligenosis is the downscaling of mature cell architecture via a process involving lysosomes. Here, we notice that sulfated glycoproteins are not only digested during paligenosis but also excreted into the gland. Various genetic and pharmacological approaches show that endoplasmic reticulum membranes and secretory granule cargo are also excreted and that the process proceeds in parallel with but is mechanistically independent of autophagy. Three-dimensional light and electron microscopy demonstrated that excretion occurs via unique, complex, multi-chambered invaginations of the apical plasma membrane. As this lysosome-independent cell cleansing process does not seem to have been priorly described, we termed it "cathartocytosis." Cathartocytosis allows a cell to rapidly eject excess material without waiting for autophagic and lysosomal digestion, providing for efficient cellular downscaling.

Keywords

Cell Differentiation, Animals, Cellular Reprogramming, Lysosomes, Autophagy, Humans, Mice, Endoplasmic Reticulum, Cell Membrane

Published Open-Access

yes

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