Mitochondria: Sovereign of inflammation?

Authors

  • Jürg Tschopp

    Corresponding author
    1. Department of Biochemistry, University of Lausanne, Center for Immunity and Infection, Epalinges, Switzerland
    • Department of Biochemistry, University of Lausanne, Center for Immunity and Infection, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland Fax:+41-21-692-5705
    Search for more papers by this author

  • Note added in proof Sadly Jürg Tschopp passed away on 22 March 2011. An Obituary can be found in this issue (Eur. J. Immunol. 2011. 41: 1189–1190). He will be greatly missed by all.

Abstract

NLRP3 inflammasome-dependent inflammatory responses are triggered by a variety of signals of host danger, including infection, tissue damage and metabolic dysregulation. How these diverse activators cause inflammasome activation is poorly understood. Recent data suggest that the mitochondria integrate these distinct signals and relay this information to the NLRP3 inflammasome. Dysfunctional mitochondria generate ROS, which is required for inflammasome activation. On the contrary, the NLRP3 inflammasome is negatively regulated by autophagy, which is a catabolic process that removes damaged or otherwise dysfunctional organelles, including mitochondria. In addition to the processing and secretion of pro-inflammatory cytokines such as IL-1β, NLRP3 inflammasome activation also influences cellular metabolic pathways such as glycolysis and lipogenesis. Mapping the connections between mitochondria, metabolism and inflammation is of great interest, as malfunctioning of this network is associated with many chronic inflammatory diseases.

Ancillary