Mitochondrial electron transport chain is necessary for NLRP3 inflammasome activation, 2022, Chandel et al.

Discussion in 'Other health news and research' started by Jaybee00, May 13, 2022.

  1. Jaybee00

    Jaybee00 Senior Member (Voting Rights)

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    Mitochondrial respiratory chain sustains inflammation

    https://medicalxpress.com/news/2022-05-mitochondrial-respiratory-chain-sustains-inflammation.html

    Northwestern Medicine investigators recently discovered that the mitochondrial respiratory chain—a series of protein complexes essential for a cellular respiration and energy production—is necessary for the activation of another protein complex linked to inflammation and the progression of chronic diseases, according to a study published in Nature Immunology.


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    Last edited by a moderator: May 13, 2022
  2. Trish

    Trish Moderator Staff Member

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    Mitochondrial electron transport chain is necessary for NLRP3 inflammasome activation
    https://www.nature.com/articles/s41590-022-01185-3

    Abstract

    The NLRP3 inflammasome is linked to sterile and pathogen-dependent inflammation, and its dysregulation underlies many chronic diseases. Mitochondria have been implicated as regulators of the NLRP3 inflammasome through several mechanisms including generation of mitochondrial reactive oxygen species (ROS).

    Here, we report that mitochondrial electron transport chain (ETC) complex I, II, III and V inhibitors all prevent NLRP3 inflammasome activation. Ectopic expression of Saccharomyces cerevisiae NADH dehydrogenase (NDI1) or Ciona intestinalis alternative oxidase, which can complement the functional loss of mitochondrial complex I or III, respectively, without generation of ROS, rescued NLRP3 inflammasome activation in the absence of endogenous mitochondrial complex I or complex III function.

    Metabolomics revealed phosphocreatine (PCr), which can sustain ATP levels, as a common metabolite that is diminished by mitochondrial ETC inhibitors. PCr depletion decreased ATP levels and NLRP3 inflammasome activation.

    Thus, the mitochondrial ETC sustains NLRP3 inflammasome activation through PCr-dependent generation of ATP, but via a ROS-independent mechanism.

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