Cell Death and Inflammation Unit, VIB Center for Inflammation Research, Ghent, Belgium.
Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
Autophagy. 2023 Sep;19(9):2585-2589. doi: 10.1080/15548627.2023.2197760. Epub 2023 Apr 9.
The (macro)autophagy field is facing a paradigm shift after the recent discovery that cytosolic cargoes can still be selectively targeted to phagophores (the precursors to autophagosomes) even in the absence of LC3 or other Atg8-protein family members. Several studies have indeed reported on the existence of an unconventional selective autophagic pathway that involves the formation of an autophagosome around the cargo through the direct selective autophagy receptor-mediated recruitment of RB1CC1/FIP200, thereby bypassing the requirement of LC3. In an article recently published in , we demonstrate the physiological importance of this unconventional autophagic pathway in the context of TNF (tumor necrosis factor) signaling. We show that it promotes the degradation of the cytotoxic TNFRSF1A/TNFR1 (TNF receptor superfamily member 1A) complex II that assembles upon TNF sensing and thereby protects mice from TNFRSF1A-driven embryonic lethality and skin inflammation. ATG: autophagy related; CASP: caspase; FIR: RB1CC1/FIP200-interacting region; LIR: LC3-interacting region; M1: linear; PAS: phagophore assembly site; PtdIns3K: phosphatidylinositol 3-kinase; TNF: tumor necrosis factor; TNFRSF1A: TNF receptor superfamily member 1A.
在最近的研究发现中，细胞质货物即使在缺乏 LC3 或其他 Atg8-蛋白家族成员的情况下，仍然可以被选择性地靶向到吞噬体（自噬体的前体），这使得（宏观）自噬领域面临着范式转变。几项研究确实报道了一种非传统的选择性自噬途径的存在，该途径涉及通过直接选择性自噬受体介导的 RB1CC1/FIP200 的募集，从而绕过 LC3 的要求，在货物周围形成自噬体。在最近发表在《细胞》杂志上的一篇文章中，我们证明了这种非传统自噬途径在 TNF（肿瘤坏死因子）信号中的生理重要性。我们表明，它促进了在 TNF 感应时组装的细胞毒性 TNFRSF1A/TNFR1（肿瘤坏死因子受体超家族成员 1A）复合物 II 的降解，从而保护小鼠免受 TNFRSF1A 驱动的胚胎致死性和皮肤炎症。ATG：自噬相关；CASP：半胱天冬酶；FIR：RB1CC1/FIP200 相互作用区；LIR：LC3 相互作用区；M1：线性；PAS：吞噬体组装位点；PtdIns3K：磷脂酰肌醇 3-激酶；TNF：肿瘤坏死因子；TNFRSF1A：肿瘤坏死因子受体超家族成员 1A。
