Department of Biophysics, Ut Southwestern Medical Center, Dallas, Tx, USA.
Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA.
Autophagy. 2022 Nov;18(11):2754-2755. doi: 10.1080/15548627.2022.2062953. Epub 2022 Apr 20.
ATG9A is essential for macroautophagy/autophagy and considered to be one of the earliest ATG (autophagy related) proteins recruited to sites of autophagosome biogenesis. Recent data suggest ATG9A vesicles may even form the lipid seed of the autophagosome. However, ATG9A regulation is still poorly understood, which is likely at least partly due to challenges inherent to studying an intracellular transmembrane protein with no apparent enzymatic activity. To help overcome these challenges, we used BioID and quantitative LC-MS/MS to map the proximity interactome of ATG9A, which included entire protein complexes involved in protein trafficking, and proteins implicated in autophagy but previously lacking any physical link to core autophagy machinery. We also unexpectedly found an ATG9A interaction with an ULK1-independent ATG13-ATG101 dimer that promotes autophagy in fed cells.
ATG9A 对于巨自噬/自噬是必不可少的，被认为是最早被招募到自噬体生物发生部位的 ATG（自噬相关）蛋白之一。最近的数据表明，ATG9A 小泡甚至可能形成自噬体的脂质种子。然而，ATG9A 的调控仍然知之甚少，这可能至少部分是由于研究一种没有明显酶活性的细胞内跨膜蛋白所固有的挑战。为了帮助克服这些挑战，我们使用 BioID 和定量 LC-MS/MS 来绘制 ATG9A 的临近互作组，其中包括涉及蛋白质运输的整个蛋白质复合物，以及与自噬相关但以前与核心自噬机制没有任何物理联系的蛋白质。我们还意外地发现了 ATG9A 与 ULK1 无关的 ATG13-ATG101 二聚体的相互作用，该二聚体促进饱食细胞中的自噬。
