In metazoans the endoplasmic reticulum (ER) undergoes extensive remodeling during the cell cycle. The endosomal sorting complexes required for transport (ESCRT) protein CHMP7 coordinates ESCRT-III dependent nuclear envelope reformation during mitotic exit. However, potential roles of ER-associated CHMP7 at non-mitotic stages remain unclear. Here we discovered a new role of CHMP7 in mediating three-way ER and ER-mitochondrial membrane contact sites (MCSs). We showed that CHMP7 localizes to multiple cellular membranes including the ER, mitochondrial-associated membranes (MAMs) and the outer mitochondrial membrane (OMM) via its N-terminal membrane-binding domain. CHMP7 undergoes dynamic assembly at three-way ER junctions and ER-mitochondrial MCSs through hydrophobic interactions among α helix-1 and α helix-2 of the C-terminal CHMP-like domain, which was required for tethering different organelles in vivo. Furthermore, CHMP7 mediates the formation of three-way ER junctions in parallel with Atlastins (ATLs). Importantly, CHMP7 also regulates ER-mitochondrial interactions and its depletion affects mitochondrial division independently of ESCRT complex. Taken together, our results suggest a direct role of CHMP7 in the formation of the ER contacts in interphase.
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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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We thank Ping Liu (the Optical Bioimaging Core Facility of WNLO-HUST), Linfang Yang (Huazhong University of Science and Technology) for imaging assistance, and Wenjun Pu (Shenzhen Bay Laboratory) for technical help with CHMP7 Halo KI.
JX was supported by National Natural Science Foundation of China (81901166). LD was supported by the Guangdong Basic and Applied Basic Research Foundation (2020A1515110542) and Shenzhen Bay Laboratory Open Fund (SZBL2020090501004). WJ was supported by National Natural Science Foundation of China (32122025; 91854109), and the Program for HUST Academic Frontier Youth Team (2018QYTD11).
The authors declare no competing interests.
All experimental procedures involving animals were approved by Animal Use and Care Committee of Huazhong University of Science and Technology, Wuhan, China. All animal care and use followed the guidelines of the Animal Care and Use Committee of Huazhong University of Science and Technology. During all procedures of experiments, the number of animals and their suffering by treatments were minimized.
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Chu, Q., Wang, J., Du, Y. et al. Oligomeric CHMP7 mediates three-way ER junctions and ER-mitochondria interactions. Cell Death Differ 30, 94–110 (2023). https://doi.org/10.1038/s41418-022-01048-2