Stomach Cells excretes Waste, Not Digest It, To Mend Injuries

Amazing stuff!

"When the stomach gets injured, the large, enzyme-secreting cells in its lining, called chief cells, can quickly reprogram themselves to become small, proliferative cells to repair the damaged tissue. Scientists once thought that this dramatic downsizing involved the destruction of the cells’ components through lysosomes ... 

But recently, a group of researchers discovered that in mice, gastric chief cells did not swallow unwanted cell debris—[but excreted it]. The team, ... named this process cathartocytosis, which means “cellular cleansing” in Greek. Their findings ... offer insights into how this novel biological phenomenon can help stomach wounds heal and if dysregulated, may lead to cancer. ..."

From the highlights and abstract:

"Highlights

• Defining cathartocytosis, an injury-induced process cells use to downscale cellular machinery

• Three-dimensional reconstruction detailing how cells reorganize organelles during paligenosis

• Cathartocytosis and autophagy occur together in paligenosis but are mechanistically distinct

• EPG5 prevents fusion of autophagic compartments with the apical membrane after injury

Summary

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."

Stomach Cells Vomit Waste, Not Digest It, To Mend Injuries | The Scientist "Scientists discovered a novel process, called cathartocytosis, where stomach cells [expel] out their contents to quickly shrink and repair damaged tissue."

Cathartocytosis: Jettisoning of cellular material during reprogramming of differentiated cells (open access)

Graphical abstract

Figure 7 Cathartocytosis model

(A) Single two-dimensional sections from FIB-SEM of chief cell apical plasma membrane at 24 h post-injury demonstrate phagophore-shaped structures (i.e., similar to emerging, double-membrane autophagosomes) contiguous with the apical invaginations (yellow arrows). Video S3 shows this section in three-dimensional context.

(B) Fusion of a zymogenic granule into an apical invagination with release of cargo as well as membrane into the lumen (pink arrowhead). Video S4 demonstrates the section in three-dimensional context.

(C) Schematic representation of canonical autophagy versus our proposed cathartocytosis process. The two processes occur concurrently after injury, and both likely combine to play a role in cellular downscaling. Magenta: cathartocytosis; gray: classical autophagy; black: lysosome; green: generic cytoplasmic organelle (granule, ER, mitochondria, etc.).