Programmed necrosis. From molecules to health and disease

Lorenzo Galluzzi, Tom Vanden Berghe, Nele Vanlangenakker, Sabrina Buettner, Tobias Eisenberg, Peter Vandenabeele, Frank Madeo, Guido Kroemer

    Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

    133 Citations (Scopus)

    Abstract

    During the past decade, cell death researchers have witnessed a gradual but deep conceptual revolution: it has been unequivocally shown that necrosis, which for long had been considered as a purely accidental cell death mode, can also be induced by finely regulated signal transduction pathways. In particular, when caspases are inhibited by pharmacological or genetic means, the ligation of death receptors such as the tumor necrosis factor receptor 1 (TNFR1) can lead to the assembly of a supramolecular complex containing the receptor-interacting protein kinases 1 and 3 (RIP1 and RIP3) that delivers a pronecrotic signal. Such complex has recently been dubbed necrosome and mediates the execution of a specific instance of regulated necrosis, necroptosis. Soon, it turned out that programmed necrosis occurs in nonmammalian model organisms and that it is implicated in human diseases including ischemia and viral infection. In this review, we first describe the historical evolution of the concept of programmed necrosis and the molecular mechanisms that underlie necroptosis initiation and execution. We then provide evidence suggesting that necroptosis represents an ancient and evolutionarily conserved cell death modality that may be targeted for drug development.

    Original languageEnglish
    Title of host publicationInternational Review of Cell and Molecular Biology
    PublisherElsevier Inc.
    Pages1-35
    Number of pages35
    DOIs
    Publication statusPublished - 1 Jan 2011

    Publication series

    NameInternational Review of Cell and Molecular Biology
    Volume289
    ISSN (Print)1937-6448
    ISSN (Electronic)1937-6448

    Keywords

    • Caspases
    • Glutaminolysis
    • Lipid peroxidation
    • NOX1
    • RIP1
    • ROS
    • TNFR

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