Lysosomal Ion Channels as Decoders of Cellular Signals

Lysosomes, the degradation center of the cell, are filled with acidic hydrolases. Lysosomes generate nutrient-sensitive signals to regulate the import of H+, hydrolases, and endocytic and autophagic cargos, as well as the export of their degradation products (catabolites). In response to environmental and cellular signals, lysosomes change their positioning, number, morphology, size, composition, and activity within minutes to hours to meet the changing cellular needs. Ion channels in the lysosome are essential transducers that mediate signal-initiated Ca2+/Fe2+/Zn2+ release and H+/Na+/K+-dependent changes of membrane potential across the perimeter membrane. Dysregulation of lysosomal ion flux impairs lysosome movement, membrane trafficking, nutrient sensing, membrane repair, organelle membrane contact, and lysosome biogenesis and adaptation. Hence, activation and inhibition of lysosomal channels by synthetic modulators may tune lysosome function to maintain cellular health and promote cellular clearance in lysosome storage disorders. Lysosomes generate nutrient-sensitive signals to regulate the import of H+, hydrolases, and endocytic and autophagic cargos, as well as the export of the degradation products. In response to environmental and cellular signals, lysosomes change their positioning, number, morphology, size, composition, and activity within minutes to hours to meet the changing cellular needs. Selective Na+, K+, and Ca2+ channels are present in the lysosome to maintain the concentration gradients of H+, Na+, K+, and Ca2+ across the lysosomal membrane. Ion channels in the lysosome are essential transducers of cellular signals and are required for cellular homeostasis. Signal-initiated lysosomal Ca2+ release and membrane potential changes regulate lysosome movement, membrane trafficking, nutrient sensing, membrane repair, organelle membrane contact, and lysosome biogenesis. Activation and inhibition of lysosomal channels may tune lysosome function to promote cellular clearance in lysosome storage disorders.