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Clathrin and phosphatidylinositol-4,5-bisphosphate regulate autophagic lysosome reformation
Abstract
Autophagy is a lysosome-based degradation pathway. During autophagy, lysosomes fuse with autophagosomes to form autolysosomes. Following starvation-induced autophagy, nascent lysosomes are formed from autolysosomal membranes through an evolutionarily conserved cellular process, autophagic lysosome reformation (ALR), which is critical for maintaining lysosome homeostasis. Here we report that clathrin and phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P(2)) regulate ALR. Combining a screen of candidates identified through proteomic analysis of purified ALR tubules, and large-scale RNAi knockdown, we unveiled a tightly regulated molecular pathway that controls lysosome homeostasis, in which clathrin and PtdIns(4,5)P(2) are the central components. Our functional study demonstrates the central role of clathrin and its associated proteins in cargo sorting, phospholipid conversion, initiation of autolysosome tubulation, and proto-lysosome budding during ALR. Our data not only uncover a molecular pathway by which lysosome homeostasis is maintained through the ALR process, but also reveal unexpected functions of clathrin and PtdIns(4,5)P(2) in lysosome homeostasis.
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Lysosomal PI(4,5)P2 serves as a signaling molecule that regulates traffic from the lysosome and mediates lysosome reformation after autophagosome fusion.
“Lysosomal PI(4,5)P2 serves as an important signaling molecule that regulates traffic from the lysosome51 and that mediates lysosome reformation after autophagosome fusion52.”
From Phosphatidylinositol-(4,5)-Bisphosphate Regulates Plasma Cholesterol Through LDL (Low-Density Lipoprotein) Receptor Lysosomal Degradation (2020) · cites this paper as [52]
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Lőrincz, P., & Juhász, G. (2020) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.10.028 · Cited by 328
Serrano‐Puebla, A., & Boya, P. (2016) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12966 · Cited by 204
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Qin, Y., Ting, F., Kim, M. J., Strelnikov, J., Harmon, J., Gao, F., Dose, A., Teng, B.-B., Alipour, M. A., Yao, Z., et al. (2020) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.120.314033 · Cited by 18
Metadata
- Authors
- Rong, Y., Liu, M., Ma, L., Du, W., Zhang, H., Tian, Y., Cao, Z., Li, Y., Ren, H., Zhang, C., Li, L., Chen, S., Xi, J., & Yu, L.
- Venue
- Nature Cell Biology
- Published
- 2012-08-12
- Volume
- 14
- Issue
- 9
- Pages
- 924-934
- ISSN
- 1465-7392
- 1476-4679
- Cited by
- 297
- References
- 6
- Language
- en
- Licence
- www.springer.com/tdm (tdm)
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