Browsing by Subject "Gasdermin"

Now showing 1 - 3 of 3
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    Evolution of the gasdermin family and pyroptosis
    (Elsevier, 2023-09-19) Angosto-Bazarra, Diego; Guijarro, Adriana; Pelegrín Vivancos, Pablo; Bioquímica y Biología Molecular B e Inmunología
    Gasdermins have been identified as playing a prominent role in the innate immune response as the executors of a specific type of cell death called pyroptosis. Specific proteolytic cleavage of gasdermins generates an N-terminal that oligomerizes and forms pores in the cell membrane. Although pyroptosis has been widely described in mammals, the importance of gasdermins and gasdermin-like proteins in inducing cell death in other vertebrates, in invertebrates and in other taxa including fungi and bacteria is still being determined. Mammalian, fungal and bacterial gasdermins have in common the fact that they go through the same stages (such as proteolytic activation) when inducing membrane rupture, which suggests that pyroptosis is as an ancient mechanism. In this review, we summarize the evolution and function of the gasdermin and gasdermin-like proteins in animals, fungi and bacteria.
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    Gasdermin D mediates a fast transient release of ATP after NLRP3 inflammasome activation before ninjurin 1-induced lytic cell death
    (Cell Press, 2025) Schachter, Julieta; Guijarro, Adriana; Angosto-Bazarra, Diego; Pinilla, Miriam; Hurtado-Navarro, Laura; Meunier, Etienne; Perez-Oliva, Ana Belen; Schwarzbaum, Pablo J; Pelegrín Vivancos, Pablo; Pinilla Marquinez, Míriam; Bioquímica y Biología Molecular B e Inmunología
    Pyroptosis is a lytic cell death triggered by the cleavage of gasdermin (GSDM) proteins and subsequent pore formation by the N-terminal domain oligomerization in the plasma membrane. GSDMD is cleaved by caspase-1/-4/-5/-11 upon inflammasome activation and mediates interleukin (IL)-1β and IL-18 release. GSDMD pores favor ninjurin 1 (NINJ1)-induced plasma membrane rupture and cell death. Here, we demonstrate that GSDMD mediates early ATP release upon NLRP3 inflammasome activation independently of NINJ1, occurring before IL-1β release and cell death and constituting an early danger signal. The release of ATP is a transient signal terminated before the cells continue to permeabilize and die. The different N termini of GSDMA to -E are also able to release ATP and induce monocyte migration toward pyroptotic cells. This study reveals ATP release as an early and transient danger signal depending on GSDMD plasma membrane permeabilization, independently of the late stages of lytic cell death.
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    Gasdermins mediate cellular release of mitochondrial DNA during pyroptosis and apoptosis
    (Wiley, 2021-08) Torre-Minguela, Carlos de; Gomez, Ana I.; Couillin, Isabelle; Pelegrín Vivancos, Pablo; Bioquímica y Biología Molecular B e Inmunología
    Pyroptosis and intrinsic apoptosis are two forms of regulated cell death driven by active caspases where plasma membrane permeabilization is induced by gasdermin pores. Caspase-1 induces gasdermin D pore formation during pyroptosis whereas caspase-3 promotes gasdermin E pore formation during apoptosis. These two types of cell death are accompanied by mitochondrial outer membrane permeabilization due to BAK/BAX pore formation in the external membrane of mitochondria, and to some extent this complex also affects the inner mitochondrial membrane facilitating mitochondrial DNA relocalisation from the matrix to the cytosol. However, the detailed mechanism responsible for this process has not been investigated. Herein, we reported that gasdermin processing is required to induce mitochondrial DNA release from cells during pyroptosis and apoptosis. Gasdermin targeted at the plasma membrane promotes a fast mitochondrial collapse along with the initial accumulation of mitochondrial DNA in the cytosol and then facilitates the DNA’s release from the cell when the plasma membrane ruptures. These findings demonstrate that gasdermin action has a critical effect on the plasma membrane and facilitates the release of mitochondrial DNA as a damage-associated molecular pattern.