Lysosome function in glomerular health and disease

Abstract

The lysosome represents an important regulatory platform within numerous vesicle trafficking pathways including the endocytic, phagocytic, and autophagic pathways. Its ability to fuse with endosomes, phagosomes, and autophagosomes enables the lysosome to break down a wide range of both endogenous and exogenous cargo, including macromolecules, certain pathogens, and old or damaged organelles. Due to its center position in an intricate network of trafficking events, the lysosome has emerged as a central signaling node for sensing and orchestrating the cells metabolism and immune response, for inter-organelle and inter-cellular signaling and in membrane repair. This review highlights the current knowledge of general lysosome function and discusses these findings in their implication for renal glomerular cell types in health and disease including the involvement of glomerular cells in lysosomal storage diseases and the role of lysosomes in nongenetic glomerular injuries.

Relationship between lysosomal dyshomeostasis and progression of diabetic kidney disease

“…Yet, lysosomes have several other important biological functions, including membrane repair, secretion, energy metabolism, and signal transduction (Fig. 1B) 1,13 .…”

“…Lysosomes are terminal degradation components that participate in the degradation of damaged cell structures, senescent organelles, and biological macromolecules, and produce small molecules (e.g., amino acids and fatty acids), which are subsequently transported to the cytoplasm for cell reuse and ATP generation to provide energy, thereby ensuring energy metabolism of cells 1,20 .…”

“…TFEB acetylation at K274 and K279 blocks TFEB nucleation [28][29][30][31]33 . B Lysosomes have several biological functions, including membrane repair, secretion, energy metabolism, and signal transduction 1,[13][14][15][16][17][18][19][20][21][22][23] . AMPK, adenosine 5′-monophosphate (AMP)-activated protein kinase; ROS, reactive oxygen species; STUB1, STIP1-homologous U-Box containing protein 1; TFEB, transcription factor EB.…”

“…Lysosomes are important regulatory platforms in numerous vesicle transport pathways, including endocytosis, phagocytosis, and autophagy. Their ability to fuse with endosomes, phagosomes, and autophagosomes enables them to break down a variety of endogenous and exogenous substances, including macromolecules, certain pathogens, and damaged organelles 1 . Owing to their central position in complex intracellular trafficking networks, lysosomes have become central signaling nodes for sensing and coordinating cellular metabolism, intra-and intercellular signaling, and membrane repair 1 .…”

The Intertwining of Autophagy and the Ubiquitin Proteasome System in Podocyte (Patho)Physiology

“…The principle of macroautophagy is that mainly bulky cargo such as less rapidly degraded proteins, organelles or protein aggregates are removed by engulfing them in a double membrane compartment called the autophagosome, which fuses with lysosomes [22] for final degradation. Lysosomal degradation is highly efficient, as this membrane-enclosed organelle contains numerous proteases of low specificity [23]. Depending on the substrates degraded, macroautophagy is subdivided in mammalian cells into a bulk non-selective form and into selective forms governing the removal of mitochondria (mitophagy), of lipid droplets (lipophagy), of peroxisomes (pexophagy), of ribosomes (ribophagy), of proteasomes (proteophagy), and of lysosomes (lysophagy) [24].…”