In eukaryotes, autophagy maintains cellular homeostasis by recycling cytoplasmic components. The autophagy-related proteins (ATGs) ATG1 and ATG13 form a protein kinase complex that regulates autophagosome formation; however, mechanisms regulating ATG1 and ATG13 remain poorly understood. Here, we show that, under different nutrient conditions, the RING-type E3 ligases SEVEN IN ABSENTIA OF ARABIDOPSIS THALIANA1 (SINAT1), SINAT2, and SINAT6 control ATG1 and ATG13 stability and autophagy dynamics by modulating ATG13 ubiquitylation in Arabidopsis (Arabidopsis thaliana). During prolonged starvation and recovery, ATG1 and ATG13 were degraded through the 26S proteasome pathway. TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR1a (TRAF1a) and TRAF1b interacted in planta with ATG13a and ATG13b and required SINAT1 and SINAT2 to ubiquitylate and degrade ATG13s in vivo. Moreover, lysines K607 and K609 of ATG13a protein contributed to K48-linked ubiquitylation and destabilization, and suppression of autophagy. Under starvation conditions, SINAT6 competitively interacted with ATG13 and induced autophagosome biogenesis. Furthermore, under starvation conditions, ATG1 promoted TRAF1a protein stability in vivo, suggesting feedback regulation of autophagy. Consistent with ATGs functioning in autophagy, the atg1a atg1b atg1c triple knockout mutants exhibited premature leaf senescence, hypersensitivity to nutrient starvation, and reduction in TRAF1a stability. Therefore, these findings demonstrate that SINAT family proteins facilitate ATG13 ubiquitylation and stability and thus regulate autophagy.

中文翻译：

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拟南芥 SINAT 蛋白通过介导 ATG13 的泛素化和降解来控制自噬。

在真核生物中，自噬通过回收细胞质成分来维持细胞稳态。自噬相关蛋白（ATG）ATG1和ATG13形成蛋白激酶复合物，调节自噬体的形成；然而，人们对 ATG1 和 ATG13 的调节机制仍知之甚少。在这里，我们发现，在不同的营养条件下，拟南芥缺氧中的环型E3连接酶SEVEN 7 (SINAT1)、SINAT2和SINAT6通过调节拟南芥(Arabidopsis thaliana)中ATG13的泛素化来控制ATG1和ATG13的稳定性和自噬动态。在长时间的饥饿和恢复过程中，ATG1 和 ATG13 通过 26S 蛋白酶体途径被降解。肿瘤坏死因子受体相关因子 1a (TRAF1a) 和 TRAF1b 在植物体内与 ATG13a 和 ATG13b 相互作用，并需要 SINAT1 和 SINAT2 在体内泛素化和降解 ATG13。此外，ATG13a 蛋白的赖氨酸 K607 和 K609 有助于 K48 连接的泛素化和不稳定，以及自噬的抑制。在饥饿条件下，SINAT6 与 ATG13 竞争性相互作用并诱导自噬体生物发生。此外，在饥饿条件下，ATG1 促进体内 TRAF1a 蛋白的稳定性，表明自噬的反馈调节。与 ATG 在自噬中的功能一致，atg1a atg1b atg1c 三重敲除突变体表现出叶片过早衰老、对营养饥饿的超敏性以及 TRAF1a 稳定性降低。所以，