The release and activity of HMGB1 in ferroptosis

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

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)278-283
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume510
Issue number2
DOIs
StatePublished - Mar 5 2019

Fingerprint

HMGB1 Protein
Autophagy
Inflammation
Acetylation
Iron Overload
Macrophages
Immune system
Chloroquine
Therapeutic Uses
Cell death
Ablation
Lipid Peroxidation
Immune System
Cell Death
Necrosis
Iron
Lipids

Keywords

  • AGER
  • Autophagy
  • DAMP
  • Ferroptosis
  • HMGB1
  • Inflammation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

The release and activity of HMGB1 in ferroptosis. / Wen, Qirong; Liu, Jiao; Kang, Rui; Zhou, Borong; Tang, Daolin.

In: Biochemical and Biophysical Research Communications, Vol. 510, No. 2, 05.03.2019, p. 278-283.

Research output: Contribution to journalArticle

Wen, Qirong ; Liu, Jiao ; Kang, Rui ; Zhou, Borong ; Tang, Daolin. / The release and activity of HMGB1 in ferroptosis. In: Biochemical and Biophysical Research Communications. 2019 ; Vol. 510, No. 2. pp. 278-283.
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