Cited by 297

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Clathrin and phosphatidylinositol-4,5-bisphosphate regulate autophagic lysosome reformation

Rong, Yueguang, Liu, Mei, Ma, Liang, Du, Wanqing, Zhang, Hanshuo, Tian, Yuan, Cao, Zhen, Li, Ying, Ren, He, Zhang, Chuanmao, Li, Lin, Chen, She, Xi, Jianzhong, Yu, Li·2012·Nature Cell Biology

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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Crossref · 10.1038/ncb2557

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Research works printed but not linked: 23

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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

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