MARCH7介导的泛素化降低ATG14的溶解度以抑制自噬,Cell Reports

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MARCH7介导的泛素化降低ATG14的溶解度以抑制自噬
Cell Reports ( IF 7.5 ) Pub Date : 2023-08-26 , DOI: 10.1016/j.celrep.2023.113045
Xue Shi ₁ , Wenfeng Wu ₂ , Zhenhuan Feng ₁ , Peiyang Fan ₃ , Ruona Shi ₄ , Xiaofei Zhang ₅

Affiliation

CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Center for Cell Lineage and Development, GIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research Centre, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510530, China.
SanQuan College, Xinxiang Medical University, Xinxiang, Henan 453003, China.
CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Center for Cell Lineage and Development, GIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research Centre, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, China.
CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Center for Cell Lineage and Development, GIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research Centre, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China; Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510530, China.

自噬是对所有真核细胞生命至关重要的基本生物过程。尽管自噬得到了越来越多的研究，但其过程如何精确协调仍然是一个悬而未决的问题。已知 ATG14 (ATG14L/Barkor) 在自噬体形成和自噬体-溶酶体融合中发挥着至关重要的作用。然而，ATG14 是如何被调控的，特别是在翻译后水平上，仍不清楚。在这里，我们报道了 MARCH7（膜相关环 CH 型指 7），一种 E3 泛素连接酶，通过泛素化 ATG14 来抑制自噬。MARCH7 显着促进 ATG14 上 K6、K11 和 K63 连接的混合多泛素化，引发 ATG14 聚集并降低其在细胞中的溶解度。从功能上讲，我们发现 MARCH7 缺失减少了聚集体样诱导结构 (ALIS) 的数量。从机制上讲，我们发现泛素化的 ATG14 与 STX17 的相互作用较少，从而抑制自噬流。总的来说，我们的研究揭示了调节自噬的机制，并提出了治疗自噬相关疾病的潜在策略。

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更新日期：2023-08-26

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