Life Sciences Institute and Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.
Autophagy. 2023 Jun;19(6):1617-1618. doi: 10.1080/15548627.2023.2187609. Epub 2023 Mar 9.
TNF (tumor necrosis factor) is an important cytokine that regulates immune responses in response to microbial infection. Two fates can be induced by TNF sensing, including activation of NFKB/NF-κB and cell death, which are mainly regulated by the formation of TNFRSF1A/TNFR1 (TNF receptor superfamily member 1A) complex I and complex II, respectively. Abnormal TNF-induced cell death leads to detrimental outcomes, underlying several human inflammatory diseases. The actions of "protective brakes", or so-called specific "cell death checkpoints", are important to prevent TNF cytotoxicity. A recent study published in characterizes novel functions of ATG9A, RB1CC1/FIP200 and TAX1BP1 as components of a previously undiscovered TNF-induced cell death checkpoint, independent of its roles in canonical macroautophagy/autophagy. Notably, this ATG9A-controlled cell-death checkpoint contributes to the prevention of inflammatory skin disease, demonstrating its crucial role in serving as a safeguard against the threat of TNF cytotoxicity.
肿瘤坏死因子（TNF）是一种重要的细胞因子，可调节对微生物感染的免疫反应。TNF 感应可诱导两种命运，包括 NFKB/NF-κB 的激活和细胞死亡，这主要由 TNFRSF1A/TNFR1（肿瘤坏死因子受体超家族成员 1A）复合物 I 和复合物 II 的形成来调节。异常的 TNF 诱导的细胞死亡导致有害的后果，是几种人类炎症性疾病的基础。“保护刹车”的作用，或者所谓的特定“细胞死亡检查点”，对于防止 TNF 细胞毒性很重要。最近发表在《自然通讯》上的一项研究，描述了 ATG9A、RB1CC1/FIP200 和 TAX1BP1 作为先前未发现的 TNF 诱导细胞死亡检查点的组成部分的新功能，该检查点独立于其在经典巨自噬/自噬中的作用。值得注意的是，这种 ATG9A 控制的细胞死亡检查点有助于预防炎症性皮肤疾病，表明其在防止 TNF 细胞毒性威胁方面的关键作用。
