Division of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Cambridge, UK.
Autophagy. 2021 Dec;17(12):3897-3907. doi: 10.1080/15548627.2021.1872240. Epub 2021 Jan 18.
Macroautophagy/autophagy is triggered by various starvation and stress conditions. The phospholipid phosphatidylinositol-3-phosphate (PtdIns3P) is essential for the formation of the autophagosome both in yeast and mammals. The class III phosphatidylinositol 3-kinase, PIK3C3C in humans or Vps34 in yeast, produces PtdIns3P by phosphorylating the 3'-OH position of phosphatidylinositol (PtdIns). In order to synthesize PtdIns3P for the initiation of autophagy, PIK3C3/Vps34 has a heterotetrameric core, the PIK3C3 complex I (hereafter complex I) composed of PIK3C3/Vps34, PIK3R4/Vps15, BECN1/Vps30, and ATG14/Atg14. A fifth component of complex I, NRBF2 in mammals and Atg38 in yeast, was found and has been characterized in the past decade. The field has been expanding from cell and structural biology to mouse model and cohort studies. Here I will summarize the structures and models of complex I binding NRBF2/Atg38, its intracellular roles, and its involvement in health and disease. Along with this expansion of the field, different conclusions have been drawn in several topics. I will clarify what has and has not been agreed, and what is to be clarified in the future.
自噬是由各种饥饿和应激条件引发的。磷脂酰肌醇-3-磷酸（PtdIns3P）对于酵母和哺乳动物中自噬体的形成都是必不可少的。III 类磷脂酰肌醇 3-激酶，人类中的 PIK3C3C 或酵母中的 Vps34，通过磷酸化磷脂酰肌醇（PtdIns）的 3'-OH 位置来产生 PtdIns3P。为了合成用于自噬起始的 PtdIns3P，PIK3C3/Vps34 具有异四聚体核心，即由 PIK3C3/Vps34、PIK3R4/Vps15、BECN1/Vps30 和 ATG14/Atg14 组成的 PIK3C3 复合物 I（简称复合物 I）。过去十年中，发现并对复合物 I 结合 NRBF2/Atg38 的第五个成分，即哺乳动物中的 NRBF2 和酵母中的 Atg38 进行了研究。该领域已经从细胞和结构生物学扩展到小鼠模型和队列研究。在这里，我将总结复合物 I 结合 NRBF2/Atg38 的结构和模型、其在细胞内的作用以及其在健康和疾病中的作用。随着该领域的扩展，在几个主题上已经得出了不同的结论。我将澄清哪些已经达成共识，哪些尚未达成共识，以及未来需要澄清的问题。
