Lysosomal Calcium in Neurodegeneration

Lysosomes are the central organelles responsible for macromolecule recycling in the cell. Lysosomal dysfunction is the primary cause of lysosomal storage diseases (LSDs), and contributes significantly to the pathogenesis of common neurodegenerative diseases. The lysosomes are also intracellular stores for calcium ions, one of the most common second messenger in the cell. Lysosomal Ca²⁺ is required for diverse cellular processes including signal transduction, vesicular trafficking, autophagy, nutrient sensing, exocytosis, and membrane repair. In this review, we first summarize some recent progresses in the studies of lysosome Ca²⁺ regulation, with a focus on the newly discovered lysosomal Ca²⁺ channels and the mechanisms of lysosomal Ca²⁺ store refilling. We then discuss how defects in lysosomal Ca²⁺ release and store maintenance cause lysosomal dysfunction and neurodegeneration.