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Decoding the Intricate Mechanism of Cell Self-Destruction at the Atomic Level
A groundbreaking discovery by scientists sheds light on the precise atomic-level mechanism through which cells orchestrate their own demise. Contrary to popular belief, cells do not simply explode when they reach the end of their life. Instead, a specific protein triggers the rupture of the cell membrane. The University of Basel researchers have recently decoded this intricate process, and their findings have been published in the esteemed journal Nature.
The self-elimination of cells is an essential process for all living organisms. When cells sustain damage or get infected by viruses or bacteria, they activate an internal “self-destruct” sequence. This crucial mechanism prevents the growth of tumors and safeguards the body from the proliferation of harmful pathogens.
Until now, it was commonly believed that cells merely burst and die when their lifespan ends. However, the Biozentrum researchers at the University of Basel, along with scientists from the University of Lausanne and the Department of Biosystems Science and Engineering (D-BSSE) at ETH Zurich, have unveiled new insights into the final stage of cell death.
In their article published in Nature, they explain how a protein called ninjurin-1 forms filaments that resemble a zipper, causing the cell membrane to open and ultimately leading to the complete disintegration of the cell. These novel findings mark a significant milestone in our understanding of cell death.
The Protein’s Role in Cell Membrane Rupture
Various signals, such as bacterial components, trigger the cell death machinery. During the final phase of this process, the cell’s protective membrane becomes compromised by minuscule pores, allowing ions to enter the cell.
Professor Sebastian Hiller, who heads a research group at the Biozentrum, University of Basel, clarifies, “The prevailing notion was that the cell swells until it finally bursts due to increasing osmotic pressure. However, we are now uncovering the true process of cell rupture. Rather than bursting like a balloon, the protein ninjurin-1 acts as a breaking point in the cell membrane, causing it to rupture at specific sites.”
Using advanced techniques such as highly sensitive microscopes and NMR spectroscopy, the scientists have unraveled the mechanism by which ninjurin-1 induces membrane rupture at the atomic level. Ninjurin-1, a small protein embedded in the cell membrane, plays a crucial role.
“When triggered, two ninjurin-1 proteins cluster together, inserting a wedge into the membrane,” explains Morris Degen, the study’s first author and a Ph.D. student at the Ph.D. School of the Swiss Nanoscience Institute. “Further proteins attach to the initial wedge, creating large lesions and holes. Consequently, the cell membrane cleaves open gradually, leading to the cell’s complete disintegration.”
The body’s natural cleaning mechanisms then remove the cellular debris.
“It is now evident that cell rupture does not occur without the involvement of ninjurin-1. While cells do experience some swelling due to the influx of ions, membrane rupture depends on the function of this protein,” adds Hiller. “These remarkable structural insights will expand the existing chapter on cell death in textbooks.”
Implications for Cell Death Therapies
A deeper understanding of cell death paves the way for the exploration of novel drug targets. Therapeutic interventions for treating cancer become conceivable, as certain tumor cells manage to evade programmed cell death.
Furthermore, premature cell death observed in neurodegenerative diseases like Parkinson’s disease or life-threatening conditions such as septic shock could potentially be addressed through drugs that interfere with this process.
Reference: “Structural basis of NINJ1-mediated plasma membrane rupture in cell death” by Morris Degen, José Carlos Santos, Kristyna Pluhackova, Gonzalo Cebrero, Saray Ramos, Gytis Jankevicius, Ella Hartenian, Undina Guillerm, Stefania A. Mari, Bastian Kohl, Daniel J. Müller, Paul Schanda, Timm Maier, Camilo Perez, Christian Sieben, Petr Broz and Sebastian Hiller, 17 May 2023, Nature.
DOI: 10.1038/s41586-023-05991-z
Frequently Asked Questions (FAQs) about cell death mechanism
What is the significance of this research on cell death?
This research provides valuable insights into the precise mechanism of cell death, highlighting the role of a specific protein called ninjurin-1 in rupturing the cell membrane. Understanding this process is crucial for developing potential therapies for cancer, neurodegenerative diseases, and other conditions related to cell death.
How do cells undergo self-destruction?
When cells become damaged or infected, they initiate an internal “self-destruct” sequence to eliminate themselves. This process, known as cell death, involves various signals and mechanisms to prevent the growth of tumors and protect the body from harmful pathogens.
How does the ninjurin-1 protein contribute to cell membrane rupture?
The ninjurin-1 protein assembles into filaments that act like a zipper, causing the cell membrane to open at specific sites. This rupture ultimately leads to the disintegration of the cell. The protein plays a crucial role in creating lesions and holes in the membrane, gradually breaking it down until the cell completely disintegrates.
What are the implications of this research for potential therapies?
This research deepens our understanding of cell death, opening up possibilities for novel drug targets. The insights gained from studying the role of ninjurin-1 in cell membrane rupture could potentially lead to therapeutic interventions for cancer treatment, addressing premature cell death in neurodegenerative diseases like Parkinson’s, and managing life-threatening conditions such as septic shock.
What techniques were used in this study?
The researchers employed advanced techniques such as highly sensitive microscopes and NMR spectroscopy to investigate the mechanism of ninjurin-1-induced membrane rupture at the atomic level. These cutting-edge tools allowed them to observe and analyze the intricate processes of cell death and protein interactions.
More about cell death mechanism
- University of Basel: Link
- University of Lausanne: Link
- Department of Biosystems Science and Engineering (D-BSSE) at ETH Zurich: Link
- Nature Journal: Link
- Research Article: “Structural basis of NINJ1-mediated plasma membrane rupture in cell death”: Link
