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Upon leaving the Golgi apparatus, the lysosomal enzyme-filled vesicle fuses with a late endosome, a relatively acidic organelle with an approximate pH of 5.5. This acidic environment causes dissociation of the lysosomal enzymes from the mannose 6-phosphate receptors.
The process of creating vesicles within the endosome is thought to be enhanced by the peculiar lipid BMP or LBPA, which is only found in late endosomes, endolysosomes or lysosomes. [12] When the endosome has matured into a late endosome/MVB and fuses with a lysosome, the vesicles in the lumen are delivered to the lysosome lumen.
Enzyme replacement therapy (ERT) for several lysosomal storage diseases relies on this pathway to efficiently direct synthetic enzymes to the lysosome where each can metabolize its particular substrate. [2] The pH in the late endosome can reach 6.0, which causes dissociation of M6P from its receptor. [1]
In the trans-Golgi a phosphodiesterase (EC 3.1.4.45) will remove the GlcNAc residue exposing the mannose 6-phosphate tag, allowing the lysosomal enzymes to bind to the CI-MPR and the CD-MPR. The MPR-lysosomal enzyme complex is translocated to a pre-lysosomal compartment, known as an endosome, in a COPII-coated vesicle.
The process of phagocytosis showing phagolysosome formation. Lysosome(shown in green) fuses with phagosome to form a phagolysosome. Membrane fusion of the phagosome and lysosome is regulated by the Rab5 protein, [1] a G protein that allows the exchange of material between these two organelles but prevents complete fusion of their membranes. [1]
Late endosomes often contain proteins characteristic of nucleosomes, mitochondria and mRNAs including lysosomal membrane glycoproteins and acid hydrolases. They are acidic (approx. pH 5.5), and are part of the trafficking pathway of mannose-6-phosphate receptors. Late endosomes are thought to mediate a final set of sorting events prior the ...
The enzymes inside of lysosomes are acid hydrolases which require an acidic environment for optimal performance. Lysosomes provide such an environment by maintaining a pH of 5.0 inside of the organelle. [37] If a lysosome were to rupture, the enzymes released would not be very active because of the cytosol's neutral pH.
PI4K2A is important in lysosomal quality control. It is the first essential enzyme of the phosphoinositide-initiated membrane tethering and lipid transport (PITT) pathway for rapid lysosomal repair. [13] Upon lysosomal membrane damage, PI4K2A is strongly recruited to lysosomes, leading to robust lysosomal PI4P production.