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. 2022 Sep 18;54(9):1379–1389. doi: 10.1038/s12276-022-00856-3

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — The biogenesis of TDEs begins with early endosomes budding inward to form the MVB, which depends on ESCRT complexes or through the ESCRT-independent pathway based on nSMase2. Subsequently, MVBs fuse with lysosomes for degradation or are docked to the cell periphery with the favor of Rab GTPases for secretion. Finally, SNARE complexes drive membrane fusion for TDE release.