Ubiquitination of exposed glycoproteins by SCF FBXO27 directs damaged lysosomes for autophagy

Significance Although lysosomes play a crucial role in autophagy, damaged lysosomes are eliminated by autophagy. The molecular mechanisms that recognize lysosomal damage in cells remain poorly understood, but ubiquitination is a known prerequisite for directing autophagic machinery to damaged lysosomes. FBXO27, a substrate-recognition subunit of the SCF (SKP1/CUL1/F-box protein) ubiquitin ligase complex, localizes to the cytosolic surface of endomembranes and binds glycoproteins. This paper reports that SCF FBXO27 ubiquitinates exposed glycoproteins normally sequestered on the lumenal surface of lysosomes following lysosomal damage, resulting in accelerated recruitment of autophagic machinery.