title: Direct uptake and degradation of DNA by lysosomes.
abstract: Lysosomes contain various hydrolases that can degrade proteins, lipids, nucleic acids and carbohydrates. We recently discovered "RNautophagy," an autophagic pathway in which RNA is directly taken up by lysosomes and degraded. A lysosomal membrane protein, LAMP2C, a splice variant of LAMP2, binds to RNA and acts as a receptor for this pathway. In the present study, we show that DNA is also directly taken up by lysosomes and degraded. Like RNautophagy, this autophagic pathway, which we term "DNautophagy," is dependent on ATP. The cytosolic sequence of LAMP2C also directly interacts with DNA, and LAMP2C functions as a receptor for DNautophagy, in addition to RNautophagy. Similarly to RNA, DNA binds to the cytosolic sequences of fly and nematode LAMP orthologs. Together with the findings of our previous study, our present findings suggest that RNautophagy and DNautophagy are evolutionarily conserved systems in Metazoa.
authors.affiliation: Department of Degenerative Neurological Diseases; National Institute of Neuroscience; National Center of Neurology and Psychiatry; Kodaira, Tokyo Japan; Department of Electrical Engineering and Bioscience; Graduate School of Advanced Science and Engineering; Waseda University; Shinjuku, Tokyo Japan.
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Hisae
authors.initials: H
authors.lastname: Kikuchi
authors.forename: Shu
authors.initials: S
authors.lastname: Aizawa
authors.forename: Akiko
authors.initials: A
authors.lastname: Furuta
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Hatanaka
authors.forename: Chiho
authors.initials: C
authors.lastname: Konya
authors.forename: Kenko
authors.initials: K
authors.lastname: Uchida
authors.forename: Keiji
authors.initials: K
authors.lastname: Wada
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kabuta
mesh_terms: D000818:Animals; D003600:Cytosol / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D055786:Gene Knockout Techniques; D006367:HeLa Cells; D006801:Humans; D052119:Lysosomal-Associated Membrane Protein 2 / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D052119:Lysosomal-Associated Membrane Protein 2; D004247:DNA
keywords: DNA; DNautophagy; LAMP-2; LAMP-2C; LAMP2; LAMP2C; RNA; RNautophagy; autophagy