Newswise — Programmed cell death is a vital biological process that facilitates the removal of aging, damaged, infected, and non-functional cells, playing a critical role in preserving the delicate balance between health and disease within the human body. Recently, a groundbreaking discovery by Dr. Alessandro Annibaldi and his team from the Center for Molecular Medicine Cologne (CMMC) at the University of Cologne has revealed a new mechanism for regulating cell death. This research sheds significant light on the importance of programmed cell death during conditions like SARS-CoV infection and skin injury. Their study titled 'Cleavage of cFLIP restrains cell death during viral infection and tissue injury and favors tissue repair' has been published in the prestigious journal Science Advances.
Cell death and tissue repair
Cell death is a fundamental process crucial for the proper functioning of the human body, as it facilitates the elimination of damaged cells and creates space for the generation of new ones. Nevertheless, an imbalance in cell death can have negative consequences, such as heightened inflammation and organ failure. To comprehend its role in different diseases and develop targeted therapeutic approaches for affected individuals, it is imperative to gain a deep understanding of the intricate molecular mechanisms that regulate cell death.
cFLIP cleavage as a novel cell death brake
A breakthrough in the understanding of cell death regulation has been achieved by Dr. Annibaldi and his research team, who identified a novel mechanism involving the molecule cFLIP. This protein plays a crucial role in safeguarding against cell death by inhibiting an important enzyme called Caspase-8, known for promoting cell death. Interestingly, cFLIP itself becomes a target of Caspase-8, undergoing cleavage at amino acid number 377 (D377).
Using cutting-edge cell and molecular biology techniques, the Annibaldi lab conducted pioneering studies in mice to investigate how cFLIP precisely controls cell death in a living organism experiencing stress. Their findings revealed that the cleavage of cFLIP at D377 is a vital molecular mechanism that limits the extent of cell death during viral infections, particularly in cases like SARS-CoV, and in response to skin injuries. Failure to cleave cFLIP leads to the stabilization of a large protein complex, which exhibits increased killing activity, posing a significant risk to the organism. Prior to this groundbreaking discovery, the significance of this cleavage event had remained elusive.
Dr. Kristel Lagunas, the lead author of the study, presented a model that suggests the activation of cell death programs during viral attacks or injuries. However, they emphasized the importance of carefully controlling the extent of cell death to avoid adverse consequences. The cleavage of cFLIP at D377 emerged as a critical limiting mechanism, ensuring that only the necessary number of cells undergo cell death and promoting the restoration of healthy conditions.
These findings not only advance our comprehension of cell death regulation but also offer potential for identifying specific genetic mutations in patients that may increase their vulnerability to the lethal effects of viral infections or skin injuries. This knowledge could pave the way for more targeted and personalized therapeutic approaches for such individuals.
RSS