A cellular protection racket: How lysosomal Ca2+ fluxes prevent kidney injury

LC3-lipidation is activated by lysosomal damage by mechanisms that are unknown and divergent from canonical autophagy. In this study, Nakamura et al, show that lysosomal damage induced by lysosomotropic agents or oxalate in renal proximal tubule cells causes lipidated LC3 to insert into the lysosomal membrane to activate TRPML1 channels and release Ca2+ from lysosomes. This leads to TFEB dephosphorylation and translocation into the nucleus which results in clearance of damaged lysosomes and their contents which may reduce the deleterious effects of crystal nephmpathy.

Automated summary

LC3-lipidation is activated by mechanisms unrelated to canonical autophagy, as this study shows that lysosomal damage induced by lysosomotropic agents or oxalate leads to TFEB dephosphorylation and translocation into the nucleus which promotes the clearance of damaged lysosomes, reducing the deleterious effects of crystal nephmpathy.