A new type of ERGIC-ERES membrane contact mediated by TMED9 and SEC12 is required for autophagosome biogenesis

• 作者: Shulin Li Rui Yan Jialu Xu Shiqun Zhao Xinyu Ma Qiming Sun Min Zhang Ying Li Jun-Jie Gogo Liu Liangyi Chen Sai Li Ke Xu Liang Ge
• 来源期刊: 细胞研究（英文版）
• 年，卷（期）: 2022,（2）
• 所属期刊栏目: ARTICLES
• 页码范围: 119-138
• 页数: 20页
• 语种: 英文

摘要

Under stress,the endomembrane system undergoes reorganization to support autophagosome biogenesis,which is a central step in autophagy.How the endomembrane system remodels has been poorly understood.Here we identify a new type of membrane contact formed between the ER-Golgi intermediate compartment (ERGIC) and the ER-exit site (ERES) in the ER-Golgi system,which is essential for promoting autophagosome biogenesis induced by different stress stimuli.The ERGIC-ERES contact is established by the interaction between TMED9 and SEC12 which generates a short distance opposition (as close as 2-5 nm) between the two compartments.The tight membrane contact allows the ERES-Iocated SEC12 to transactivate COPⅡ assembly on the ERGIC.In addition,a portion of SEC12 also relocates to the ERGIC.Through both mechanisms,the ERGIC-ERES contact promotes formation of the ERGIC-derived COPⅡ vesicle,a membrane precursor of the autophagosome.The ERGIC-ERES contact is physically and functionally different from the TFG-mediated ERGIC-ERES adjunction involved in secretory protein transport,and therefore defines a unique endomembrane structure generated upon stress conditions for autophagic membrane formation.