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.

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

State Key Laboratory of Membrane Biology,Beijing,China;Tsinghua-Peking Center for Life Sciences,Beijing,China;School of Life Sciences,Tsinghua University,Beijing,China;Department of Chemistry,University of California,Berkeley,CA,USA;Beijing Advanced Innovation Center for Structural Biology,Beijing,China;Beijing Key Laboratory of Cardiometabolic Molecular Medicine,Institute of Molecular Medicine,Peking University,Beijing,China;National Center for Nanoscience and Technology,Beijing,China;Department of Biochemistry,Department of Cardiology of Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,Zhejiang,China

细胞研究（英文版）

[1]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-.A new type of ERGIC-ERES membrane contact mediated by TMED9 and SEC12 is required for autophagosome biogenesis)[J].细胞研究（英文版）,2022(02):119-138

ERGIC,ERES,TMED9,SEC12,endomembrane,remodels,Iocated,transactivate,relocates,adjunction

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