Study Uncovers Details About Cells' “Self-Destruction’ Mechanism

Researchers have uncovered details about how infected or damaged cells eliminate themselves by starting a built-in ''suicide'' program and that a specific protein, called ninjurin-1, serves as a breaking point for cell membrane rupture.

They found that ninjurin-1 assembles into filaments that work like a zipper and open the cell membrane, thus leading to the disintegration of the cell.

Publishing their results in the journal Nature, the researchers from University of Basel, the University of Lausanne and ETH Zurich, Switzerland, have provided new insights into the final step of cell death, which prevents the development of tumors and the spread of pathogens in the body and is crucial for all organisms.

Every day, millions of cells die in our body and contrary to what is generally assumed, cells do not simply burst at the end of their lives, they say.

Various signals, such as bacterial components, trigger the cell death machinery at the final stage of which, 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,'' explained 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,'' said Hiller.

Using highly sensitive microscopes and nuclear magnetic resonance spectroscopy, the scientists have elucidated the cells' destruction mechanism by which ninjurin-1, a small protein embedded in the cell membrane, induces membrane rupture at the level of individual atoms.

They found that upon receiving the suicide command, two ninjurin-1 proteins initially clustered together and drove a wedge into the membrane. ''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,'' explained Morris Degen, first author of the study.

''The cell debris is then removed by the body's own cleaning service,'' said Degen.

''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,'' said Hiller.

Since some tumour cells have been known to evade programmed cell death, this deeper understanding of cell death could facilitate therapeutic interventions to treat cancer.

On the other hand, interfering with premature cell death observed in neurodegenerative diseases such as Parkinson's disease through drugs could be a potential treatment option.