Mol Cell 封面论文：王晓东院士团队揭示程序性坏死引发炎症的新机制

Core Viewpoint - The study reveals that MLKL activates the cGAS-STING pathway by releasing mitochondrial DNA (mtDNA) during necroptosis, leading to the upregulation of interferon β (Ifnb) expression and inflammation, independent of cell membrane rupture [3][10]. Group 1: Mechanism of Necroptosis - Necroptosis is a pro-inflammatory and lytic form of programmed cell death executed by the MLKL protein, which is phosphorylated by RIPK3, causing membrane rupture and the release of damage-associated molecular patterns (DAMPs) [2]. - Phosphorylated MLKL (pMLKL) also translocates to mitochondria, inducing microtubule-dependent mtDNA release, which activates the cGAS-STING pathway [7][8]. - The integrity of microtubules is essential for the release of mtDNA into the cytoplasm [8]. Group 2: Implications for Inflammatory Bowel Disease (IBD) - In a mouse model of IBD mediated by necroptosis, inhibiting the STING pathway accelerates the resolution of intestinal inflammation [3][10]. - The study enhances understanding of necroptosis and its implications for IBD treatment, suggesting that targeting the cGAS-STING pathway may provide therapeutic benefits [10].