Portland Press

Figure 4

Lysosomal Ca2+ efflux through TRPML1 activates the Ca2+-dependent phosphatase calcineurin, which mediates dephosphorylation-dependent nuclear translocation of TFEB. Nuclear TFEB up-regulates the transcription of genes involved in lysosome biogenesis and autophagy, thereby enhancing autophagic flux. In addition, Ca2+ efflux from peripheral lysosomes promotes lysosomal exocytosis and the secretion of non-degraded materials.

Cellular effects of TFEB that might be of therapeutic benefit in lysosomal storage disorders

Lysosomal Ca²⁺ efflux through TRPML1 activates the Ca²⁺-dependent phosphatase calcineurin, which mediates dephosphorylation-dependent nuclear translocation of TFEB. Nuclear TFEB up-regulates the transcription of genes involved in lysosome biogenesis and autophagy, thereby enhancing autophagic flux. In addition, Ca²⁺ efflux from peripheral lysosomes promotes lysosomal exocytosis and the secretion of non-degraded materials.

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