Work

Programmed Necrosis in the Cross Talk of Cell Death and Inflammation

Year: 2014

Type: review

Abstract: Cell proliferation and cell death are integral elements in maintaining homeostatic balance in metazoans. Disease pathologies ensue when these processes are disturbed. A plethora of evidence indicates that malfunction of cell death can lead to inflammation, autoimmunity, or immunodeficiency. Programmed necrosis or necroptosis is a form of nonapoptotic cell death driven by the receptor interacting protein kinase 3 (RIPK3) and its substrate, mixed lineage kinase domain-like (MLKL). RIPK3 partners with its upstream adaptors RIPK1, TRIF, or DAI to signal for necroptosis in response to death receptor or Toll-like receptor stimulation, pathogen infection, or sterile cell injury. Necroptosis promotes inflammation through leakage of cellular contents from damaged plasma membranes. Intriguingly, many of the signal adaptors of necroptosis have dual functions in innate immune signaling. This unique signature illustrates the cooperative nature of necroptosis and innate inflammatory signaling pathways in managing cell and organismal stresses from pathogen infection and sterile tissue injury.

Source: Annual Review of Immunology

DOI: 10.1146/annurev-immunol-032414-112248

Authors: Francis Ka-Ming Chan, Nivea Farias Luz, Kenta Moriwaki

Institutions: University of Massachusetts Chan Medical School, Universidade Federal da Bahia, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz

Language: English

Topic: Cell death mechanisms and regulation

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Conselho Nacional de Desenvolvimento Científico e Tecnológico, National Institutes of Health, National Institute of Allergy and Infectious Diseases