Direct uptake and degradation of DNA by lysosomes

Lysosomes contain various hydrolases that can degrade proteins, lipids, nucleic acids and carbohydrates. We recently discovered "RN autophagy," an autophagic pathway in which RN A is directly taken up by lysosomes and degraded. A lysosomal membrane protein, LAMP2C, a splice variant of LAMP2, binds to RN A and acts as a receptor for this pathway. In the present study, we show that DN A is also directly taken up by lysosomes and degraded. Like RN autophagy, this autophagic pathway, which we term "DN autophagy," is dependent on ATP. The cytosolic sequence of LAMP2C also directly interacts with DN A, and LAMP2C functions as a receptor for DN autophagy, in addition to RN autophagy. Similarly to RN A, DN A binds to the cytosolic sequences of fly and nematode LAMP orthologs. Together with the findings of our previous study, our present findings suggest that RN autophagy and DN autophagy are evolutionarily conserved systems in Metazoa.