Lysosome Biogenesis and Autophagy

Lysosomes degrade biological components acquired by endocytosis, the major cellular pathway for internalization of extracellular material, and macroautophagy. This chapter presents an overview of these two major degradative intracellular pathways, and highlights the emerging cross talks between them, in healthy and diseased conditions. The pathways to lysosomes include the biosynthetic transport routes, endocytic pathways, and the autophagy pathways. The central actors of the autophagy process are the ATG genes. Based on their organization in complexes and interactions, the ATG genes have been divided into many functional clusters that compose the core autophagy machinery. Cross talk between the endocytic and autophagic pathways occurs at many levels: transcriptional regulation, protein sharing, and compartmental connections. The chapter focuses on the fusion and fission events between compartments of the endolysosomal system and autophagic membranes, respectively. Lysosome-related disorders are caused by mutations in genes encoding for proteins that directly affect lysosomal functioning, including lysosomal hydrolases and lysosomal membrane proteins.