Journal
AUTOPHAGY
Volume 11, Issue 12, Pages 2375-2376Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2015.1106668
Keywords
autophagic lysosome reformation; lysosome; MTOR; phosphatidylinositol 3-phosphate; tubulation; UVRAG; VPS34
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Funding
- MRC [MC_UP_A500_1019, MC_UU_12016/4] Funding Source: UKRI
- Medical Research Council [MC_UU_12016/4, MC_UP_A500_1019] Funding Source: Medline
- Medical Research Council [MC_UU_12016/4, 1646339, MC_UP_A500_1019] Funding Source: researchfish
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A key point in starvation-induced autophagy occurs at the end of the process, where lysosomes are regenerated from autolysosomes through a pathway termed autophagic lysosome reformation (ALR). ALR occurs when autolysosomal MTOR becomes reactivated by amino acids derived from the autophagic delivery of protein cargo. This activation not only turns off autophagosome formation but also leads to reformation of lysosomes, ready for the next round of autophagy, through a series of events involving autolysosomal tubulation. We have now found that MTOR regulates multiple steps of ALR including direct activation of the PIK3C3-UVRAG lipid kinase complex to enable autolysosomal tubules to break away and regenerate lysosomes.
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