التفاصيل البيبلوغرافية
| العنوان: |
The septin modifier, forchlorfenuron, activates NLRP3 via a potassium-independent mitochondrial axis. |
| المؤلفون: |
Holley, Caroline L.1 (AUTHOR) holley@mpiib-berlin.mpg.de, Emming, Stefan1 (AUTHOR), Monteleone, Mercedes M.1 (AUTHOR), Mellacheruvu, Manasa1 (AUTHOR), Kenney, Kirsten M.1 (AUTHOR), Lawrence, Grace M.E.P.1 (AUTHOR), Coombs, Jared R.1 (AUTHOR), Burgener, Sabrina S.1 (AUTHOR), Schroder, Kate1 (AUTHOR) k.schroder@imb.uq.edu.au |
| المصدر: |
Cell Chemical Biology. May2024, Vol. 31 Issue 5, p962-962. 1p. |
| مصطلحات موضوعية: |
*NLRP3 protein, *RESPIRATION, *CYTOSKELETAL proteins, *MITOCHONDRIA, *MITOCHONDRIAL membranes, *MEMBRANE potential, *POTASSIUM channels |
| مستخلص: |
The Nod-like receptor protein 3 (NLRP3) inflammasome is activated by stimuli that induce perturbations in cell homeostasis, which commonly converge on cellular potassium efflux. NLRP3 has thus emerged as a sensor for ionic flux. Here, we identify forchlorfenuron (FCF) as an inflammasome activator that triggers NLRP3 signaling independently of potassium efflux. FCF triggers the rearrangement of septins, key cytoskeletal proteins that regulate mitochondrial function. We report that FCF triggered the rearrangement of SEPT2 into tubular aggregates and stimulated SEPT2-independent NLRP3 inflammasome signaling. Similar to imiquimod, FCF induced the collapse of the mitochondrial membrane potential and mitochondrial respiration. FCF thereby joins the imidazoquinolines as a structurally distinct class of molecules that triggers NLRP3 inflammasome signaling independent of potassium efflux, likely by inducing mitochondrial damage. [Display omitted] • Forchlorfenuron (FCF) activates the inflammasome in human and murine macrophages • FCF triggers the canonical NLRP3 inflammasome independently of K+ efflux • Septin-2 is dramatically rearranged by FCF but is dispensable for NLRP3 activation • FCF disrupts the mitochondrial network and ablates mitochondrial respiration NLRP3 is widely regarded as a sensor for ionic flux because most NLRP3 activators do so via potassium efflux. Holley, Emming et al. report that the septin modifier FCF induces septin-2 rearrangement and NLRP3 signaling. FCF joins the imidazoquinolines as small-molecule potassium-independent NLRP3 activators that induce mitochondrial collapse. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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