Fig. 2: Mechanisms of autophagy machinery recruitment to damaged lysosomes. | Cell Discovery

Fig. 2: Mechanisms of autophagy machinery recruitment to damaged lysosomes.

From: Lysosome biology in autophagy

Fig. 2

Extensive damage to the lysosomal membrane allows cytosolic proteins to pass through freely, including glycan-binding galectins and ubiquitin ligases. Damaged lysosomes are heavily ubiquitinated, which is carried out by ubiquitylation enzymes such as UBE2QL1 (an E2 enzyme), TRIM16 (an E3 ligase) and SCFFBOX27 (an E3 ligase). K48-linked ubiquitin chains are removed by the p97-YOD1-UBXD1-PLAA complex to emphasise the presence of K63-linked chains, which are preferred by the autophagy machinery. Autophagy adaptors bind either directly to galectins (e.g. NDP52) or to ubiquitin (e.g. p62, OPTN, TAX1BP1). They then recruit the autophagy machinery, including the initiation complex, and serve to promote the formation of the autophagosome specifically around the damaged lysosome.

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