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.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
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 Ldoi
10.1038/ncb2557subject
Has Abstractpub_date
2012-09-01 00:00:00pages
924-34issue
9eissn
1465-7392issn
1476-4679pii
ncb2557journal_volume
14pub_type
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