Theranostics 2021; 11(2):974-995. doi:10.7150/thno.51871 This issue

Research Paper

Molecular machineries and physiological relevance of ER-mediated membrane contacts

Shiyin Lin1,2,*, Tian Meng1,2,*, Haofeng Huang1, Haixia Zhuang1, Zhengjie He1,2, Huan Yang3,✉, Du Feng1,2,✉

1. Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, 511436, Guangzhou, China.
2. State Key Laboratory of Respiratory Disease, Guangzhou Medical University, 511436, Guangzhou, China.
3. Department of Pulmonary and Critical Care Medicine, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410021, China.
*These authors contributed equally to this paper.

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Lin S, Meng T, Huang H, Zhuang H, He Z, Yang H, Feng D. Molecular machineries and physiological relevance of ER-mediated membrane contacts. Theranostics 2021; 11(2):974-995. doi:10.7150/thno.51871. Available from

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Graphic abstract

Membrane contact sites (MCSs) are defined as regions where two organelles are closely apposed, and most MCSs associated with each other via protein-protein or protein-lipid interactions. A number of key molecular machinery systems participate in mediating substance exchange and signal transduction, both of which are essential processes in terms of cellular physiology and pathophysiology. The endoplasmic reticulum (ER) is the largest reticulum network within the cell and has extensive communication with other cellular organelles, including the plasma membrane (PM), mitochondria, Golgi, endosomes and lipid droplets (LDs). The contacts and reactions between them are largely mediated by various protein tethers and lipids. Ions, lipids and even proteins can be transported between the ER and neighboring organelles or recruited to the contact site to exert their functions. This review focuses on the key molecules involved in the formation of different contact sites as well as their biological functions.

Keywords: MAM, MCS, Mitochondria, ER, Autophagy, Lipid droplet, Golgi, MVB, Endosome