Fig. 2: Lysosomal quality control.
From: Lysosomal quality control of cell fate: a novel therapeutic target for human diseases
Lysosomal quality control includes lysosomal repair, lysophagy, and lysosomal regeneration. The damaged lysosomal membrane can be repaired by Hsp70 and ESCRT. In lysophagy, damaged lysosomes are ultimately transported to normal lysosomes for degradation through phagosomes formed by phagophores. Two pathways for damaged lysosomes have been identified: Gals and SCFFBXO27. After binding with TRIM16, Gal3 accumulates at damaged lysosomes and recruits ULK1, Beclin 1, and ATG16L1. Then, Gal3 is modified by the K63 ubiquitin chain and binds to LC3 on the phagophore via p62. Gal8 accumulates at damaged lysosomes and binds to LC3 on the phagophore via NDP52. SCFFBXO27 is recruited to damaged lysosomes and ubiquitinates LAMP2, thereby binding to LC3 on the phagophore via p62. In addition, the inhibition of mTORC1 by the loss of lysosomes can enable TFEB to bind with CLEAR and promote lysosomal generation.
