read_status: read
type: paper
title: "Cathartocytosis: Jettisoning of cellular material during reprogramming of differentiated cells"
year: 2025
authors:
- "Brown, Jeffrey W."
- "Lin, Xiaobo"
- "Nicolazzi, Gabriel Anthony"
- "Liu, Xuemei"
- "Nguyen, Thanh"
- "Radyk, Megan D."
- "Burclaff, Joseph"
- "Mills, Jason C."
journal: "Cell Reports"
doi: "10.1016/j.celrep.2025.116070"
url: "https://linkinghub.elsevier.com/retrieve/pii/S2211124725008411"
project:
- EpPathobio
system:
- gastric_epithelium
- chief_cells
- apical_membrane
- endoplasmic_reticulum
- lysosome
disease:
- gastric_metaplasia
- tissue_injury
genes:
- epg5
- rab7
- lamp2
- atf3
processes:
- paligenosis
- cellular_downscaling
- autophagy
- organelle_extrusion
- membrane_invagination
methods:
- fib_sem
- confocal_microscopy
- immunohistochemistry
- lectin_staining
- genetic_knockout
key_findings:
- apical_organelle_excretion
- autophagy_independent_secretion
- apical_membrane_remodeling
- lysosome_membrane_mislocalization
limitations:
- unknown_molecular_mechanism
- lack_of_in_vitro_model
- limited_cell_type_scope
relevance:
- regenerative_reprogramming
- novel_secretory_mechanism
- cell_plasticity_model
concepts:
- cathartocytosis
- paligenosis
- secretory_autophagy
- apical_membrane_trafficking
tags:
- gi_regeneration
- cell_plasticity
- organelle_trafficking
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.
Injury (high does of tamoxifen) induces apical extrusion of ER and secretory granules from gastric chief cells.
This excretory pathway operates in parallel to, but independently of, canonical autophagy.
Excreted material exits through a stable, interconnected apical membrane invagination network.
Loss of EPG5 causes aberrant fusion of late endosome/lysosome membranes with the apical surface.
Cathartocytosis enables rapid cellular downscaling during paligenosis.
Focused ion beam scanning electron microscopy (FIB-SEM) for 3D ultrastructure.
Confocal immunofluorescence of apical membrane (PNA lectin).
Genetic knockout models (Epg5−/−, Gnptab−/−).
Pharmacological lysosome inhibition (hydroxychloroquine).
Glycoprotein tracking with Das-1 antibody and azure A staining
Introduces cathartocytosis as a new class of secretory behavior distinct from merocrine, apocrine, or exosomal secretion.
Reframes paligenosis as supported by dual clearance systems: autophagy + direct organelle expulsion.
Suggests epithelial cells can transiently repurpose the apical membrane into a disposal organelle.
Positions organelle jettisoning as an active, regulated remodeling process, not passive damage.
Figure 1: Sulfated glycoproteins and ER material appear in gland lumen during paligenosis.
Figure 2: FIB-SEM reveals apical membrane invaginations containing excreted organelles.
Figure 3: Confocal microscopy validates apical membrane distortion.
Figure 4–5: Epg5−/− mice show lysosome–apical membrane fusion.
Figure 7: Model contrasting autophagy with cathartocytosis.
Molecular machinery driving cathartocytosis is undefined.
No in vitro or organoid model of paligenosis available.
Generality across other tissues and cell types untested.
Cytoskeletal regulators of membrane invaginations unresolved.