MSGID: 1:317/3 646c4175   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    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   
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   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   
      
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   Story Source: Materials provided by University_of_Basel. Original written   
   by Katrin Bu"hler.   
      
   Note: Content may be edited for style and length.   
      
      
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   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   
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   Link to news story:   
   https://www.sciencedaily.com/releases/2023/05/230522131334.htm   
      
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