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The release and activity of HMGB1 in ferroptosis

Wen, Qirong ; Liu, Jiao ; Kang, Rui ; Zhou, Borong ; Tang, Daolin

Biochemical and biophysical research communications, 2019-03, Vol.510 (2), p.278-283 [Periódico revisado por pares]

United States: Elsevier Inc

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  • Título:
    The release and activity of HMGB1 in ferroptosis
  • Autor: Wen, Qirong ; Liu, Jiao ; Kang, Rui ; Zhou, Borong ; Tang, Daolin
  • Assuntos: AGER ; Autophagy ; DAMP ; Ferroptosis ; HMGB1 ; Inflammation
  • É parte de: Biochemical and biophysical research communications, 2019-03, Vol.510 (2), p.278-283
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
  • Descrição: Damage-associated molecular pattern molecules (DAMPs) are endogenous danger signals that alert the innate immune system and shape the inflammation response to cell death. However, the release and activity of DAMPs in ferroptosis, a recently identified form of regulated necrosis characterized by iron overload and lipid peroxidation, still remain poorly understood. Here, we demonstrate that HMGB1 is a DAMP released by ferroptotic cells in an autophagy-dependent manner. Both type I and II ferroptosis activators, including erastin, sorafenib, RSL3, and FIN56, induce HMGB1 release in cancer and noncancer cells. In contrast, genetic ablation (using ATG5−/− or ATG7−/− cells) or pharmacologic inhibition (the administration of bafilomycin A1 or chloroquine) of autophagy was found to block ferroptosis activator-induced HMGB1 release. Mechanically, autophagy-mediated HDAC inhibition promotes HMGB1 acetylation, resulting in HMGB1 release in ferroptosis. Moreover, AGER, but not TLR4, is required for HMGB1-mediated inflammation in macrophages in response to ferroptotic cells. These studies suggest that HMGB1 inhibition might have some potential therapeutic effects in ferroptosis-associated human disease. •Ferroptosis activators induce HMGB1 release.•Autophagy promotes HMGB1 release in ferroptosis.•Autophagy promotes HMGB1 acetylation in ferroptosis.•HMGB1-AGER pathway mediates inflammation response in ferroptosis.
  • Editor: United States: Elsevier Inc
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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