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Fig. 11. An autophagic contribution is required for the formation of phospholipid and cholesterol-rich MLBs. (A) Extensive interaction occurs between the endocytic (black) and autophagic (red) pathways. Maturation of autolysosomes into MLBs requires lysosomal degradation and is inhibited by leupeptin. U18666A-mediated lysosomal cholesterol accumulation (+U) induces the formation of cholesterol-rich MLBs from autolysosomes or pre-existing phospholipid-rich MLBs independently of lysosomal degradation (blue). (B) Upon inhibition of autophagy with 3-MA, the formation of phospholipid-rich MLBs is inhibited and U18666A-mediated lysosomal cholesterol accumulation results in the formation, not of MLBs, but of non-lamellar lysosomal vacuoles.





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