Practice question

Lysosomes are terminal degradative compartments of endocytic and autophagic pathways, acidified to pH 4.5-5.5 by vacuolar V-ATPase multi-subunit proton pump consuming ATP to pump protons into lumen generating electrochemical gradient used for secondary active transport of metabolites. They contain soluble acid hydrolases including acid phosphatase marker enzyme, cathepsin B, D, L proteases, sulfatases, beta-hexosaminidase, lipases, and nucleases delivered from trans-Golgi network via mannose-6-phosphate receptor M6PR pathway binding GlcNAc-1-phosphotransferase modified N-glycans. Endocytosed cargo internalized via clathrin coated pits, caveolin vesicles, or macropinocytosis traverses early endosomes Rab5 positive with PI3P, late endosomes Rab7 positive with lysobisphosphatidic acid, then fuses with lysosomes forming endolysosomes where hydrolysis releases amino acids, monosaccharides, fatty acids exported via cystinosin and other transporters for reuse supporting growth and signaling. Macroautophagy induced by starvation forms double membrane autophagosomes via ULK1, Beclin1, ATG machinery engulfing damaged mitochondria and aggregates, fusing with lysosomes for clearance. Defects cause lysosomal storage diseases like Tay-Sachs, Pompe, and Gaucher illustrating central importance.