Glycine inhibits NINJ1 membrane clustering to suppress plasma membrane rupture in cell death

• DOI: 10.7554/elife.78609
• Publication Date: 2022-12-05T11:16:16Z
• Authors: Jazlyn P Borges; Ragnhild SR Sætra; Allen Volchuk; Marit Bugge; Pascal Devant; Bjørnar Sporsheim; Bridget R Kilburn; Charles L Evavold; Jonathan C Kagan; Neil M Goldenberg; Trude Helen Flo; Benjamin Ethan St...
• Keywords: Pyroptosis; Cytoprotection

First recognized more than 30 years ago, glycine protects cells against rupture from diverse types of injury. This robust and widely observed effect has been speculated to target a late downstream process common multiple modes tissue The molecular that mediates cytoprotection, however, remains elusive. Here, we show works at the level NINJ1, newly identified executioner plasma membrane in pyroptosis, necrosis, post-apoptosis lysis. NINJ1 is thought cluster within cause cell rupture. We demonstrate execution pyroptotic similar for human mouse knockout functionally morphologically phenocopies cytoprotection macrophages undergoing lytic death. Next, prevents clustering by either direct or indirect mechanisms. In preserves cellular integrity but does not affect upstream inflammasome activities accompanying energetic By positioning as target, our data resolve long-standing mechanism glycine-mediated cytoprotection. new understanding will inform development preservation strategies counter pathologic