Anti-alcoholism drug disulfiram inhibits PANoptosis by blocking mitochondrial permeabilization in macrophages.

ABSTRACT:

Introduction

PANoptosis is a form of inflammatory cell death that exhibits simultaneous activation of pyroptosis, apoptosis and necroptosis signaling. Disulfiram is a clinically used anti-alcoholism drug and can inhibit NLRP3 inflammasome activation and pyroptosis. However, it is unknown whether and how disulfiram interferes with PANoptosis and related inflammatory diseases.

Methods

PANoptosis was induced in murine macrophages and related protein levels were assayed by immunoblotting. The effects of disulfiram on PANoptosis were assessed both in macrophages in vitro and in a mouse model of hemophagocytic lymphohistiocytosis (HLH) in vivo.

Results

Mitochondrial permeabilization preceded lytic cell death upon PANoptosis and binding of GSDMD-NT, GSDME-NT an

SUBMITTER: Li YP 

PROVIDER: S-EPMC12757373 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature