(macrophagy)自噬领域在最近的发现之后正在经历一次模式转变，即便没有LC3或其他Atg8蛋白家族成员的存在，细胞负载物仍然可以有选择地针对吞噬体(自噬前体)进行定向。在体外研究中，确实报告了一种非传统的选择性自噬途径，该途径涉及通过直接选择性自噬受体介导的RB1CC1/FIP200招募在负载物周围形成自噬体，从而绕过LC3的要求。在最近发表的《科学》杂志中，我们证明了该非传统自噬途径在TNF(肿瘤坏死因子)信号传导的背景下的生理重要性。我们展示它能够促进TNFRSF1A/TNFR1(肿瘤坏死因子受体超家族成员1A)复合物II的降解，并因此保护小鼠免受TNFRSF1A驱动的胚胎死亡和皮肤炎症的影响。缩写：ATG：自噬相关；CASP：半胱氨酸蛋白酶；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。

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 in vitro studies have indeed reported on the existence of an unconventional selective autophagic pathway that involves the in-situ 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 Science, 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.Abbreviations: 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.