Under control to the very end -- how our cells kill themselves

Date:
May 22, 2023
Source:
University of Basel
Summary:
Every day, millions of cells die in our body. Other than generally
assumed, cells do not simply burst at the end of their lives but
rather, a specific protein serves as a breaking point for cell
membrane rupture.

Researchers have now been able to elucidate the exact mechanism
at the atomic level.


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FULL STORY ========================================================================== Every day, millions of cells die in our body. Other than generally
assumed, cells do not simply burst at the end of their lives but
rather, a specific protein serves as a breaking point for cell membrane rupture. Researchers at the University of Basel have now been able to
elucidate the exact mechanism at the atomic level. They have published
their results in Nature.

Cell death is crucial for all organisms. Damaged cells or cells infected
with viruses or bacteria eliminate themselves by starting a built-in
"suicide" program, which prevents the development of tumors and the
spread of pathogens in the body.

Until recently, it was assumed that cells simply burst and die at the
end of their life. Now, researchers at the Biozentrum of the University
of Basel, the University of Lausanne and the Department of Biosystems
Science and Engineering (D-BSSE) at ETH Zurich have provided new insights
into the final step of cell death. In the scientific journal "Nature,"
they describe how a protein called ninjurin-1 assembles into filaments
that work like a zipper and open the cell membrane, thus leading to the disintegration of the cell. The new insights are an important milestone
in the understanding of cell death.

Protein acts as a breaking point in the cell membrane Various signals,
such as bacterial components, trigger the cell death machinery. At the
final stage of this process, the cell's protective membrane is compromised
by tiny pores which allow ions to stream into the cell. "The common understanding was that the cell then swells until it finally bursts due
to increasing osmotic pressure," explains Professor Sebastian Hiller who
heads a research group at the Biozentrum, University of Basel. "We are
now resolving how the cells really rupture. Instead of bursting like a
balloon, the protein ninjurin-1 provides a breaking point in the cell
membrane, causing rupture at specific sites." Using advanced techniques
such as highly sensitive microscopes and NMR spectroscopy, the scientists
have been able to elucidate the mechanism by which ninjurin-1 induces
membrane rupture at the level of individual atoms. Ninjurin- 1 is a
small protein embedded in the cell membrane.

"Upon receiving the suicide command, two ninjurin-1 proteins initially
cluster together and drive a wedge into the membrane," explains Morris
Degen, first author of the study and PhD student at the PhD School of
the Swiss Nanoscience Institute. "Large lesions and holes are formed by
many further proteins attaching to the initial wedge. In this way, the
cell membrane is cleaved open piece by piece until the cell disintegrates completely." The cell debris is then removed by the body's own cleaning service.

"It is now evident that the cells do not burst without ninjurin-1. They
do swell to a certain extend due to the influx of ions, but membrane
rupture is contingent on the function of this protein," adds Hiller. "The textbooks chapter on cell death will be expanded with these beautiful structural insights." Therapy to prevent or promote cell death The
deeper understanding of cell death will facilitate the search for novel
drug targets. Therapeutic interventions to treat cancer are conceivable,
since some tumor cells evade programmed cell death. Also, in the case
of premature cell death observed in neurodegenerative diseases such as Parkinson's disease or in life-threatening conditions such as septic
shock, drugs that interfere in this process are a potential treatment
option.

* RELATED_TOPICS
o Health_&_Medicine
# Stem_Cells # Lung_Cancer # Sickle_Cell_Anemia # Lymphoma
o Plants_&_Animals
# Cell_Biology # Molecular_Biology # Genetics #
Biotechnology
* RELATED_TERMS
o Necrosis o Somatic_cell o Natural_killer_cell o Cell_membrane
o Stem_cell o Adult_stem_cell o T_cell o Chemotherapy

========================================================================== Story Source: Materials provided by University_of_Basel. Original written
by Katrin Bu"hler.

Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Morris Degen, Jose' Carlos Santos, Kristyna Pluhackova, Gonzalo
Cebrero,
Saray Ramos, Gytis Jankevicius, Ella Hartenian, Undina Guillerm,
Stefania A. Mari, Bastian Kohl, Daniel J. Mu"ller, Paul Schanda,
Timm Maier, Camilo Perez, Christian Sieben, Petr Broz, Sebastian
Hiller. Structural basis of NINJ1-mediated plasma membrane rupture
in cell death. Nature, 2023; DOI: 10.1038/s41586-023-05991-z ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/05/230522131334.htm

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