Direct uptake and degradation of DNA by lysosomes

被引:111
作者
Fujiwara, Yuuki [1 ,2 ]
Kikuchi, Hisae [1 ]
Aizawa, Shu [1 ]
Furuta, Akiko [1 ]
Hatanaka, Yusuke [1 ]
Konya, Chiho [1 ]
Uchida, Kenko [2 ]
Wada, Keiji [1 ]
Kabuta, Tomohiro [1 ]
机构
[1] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Degenerat Neurol Dis, Kodaira, Tokyo 1870031, Japan
[2] Waseda Univ, Dept Elect Engn & Biosci, Grad Sch Adv Sci & Engn, Shinjuku Ku, Tokyo, Japan
基金
日本学术振兴会;
关键词
LAMP2; LAMP-2; LAMP2C; LAMP-2C; autophagy; RNA; RNautophagy; DNA; DNautophagy; CHAPERONE-MEDIATED AUTOPHAGY; MITOCHONDRIAL-DNA; RNA; PROTEINS; RECEPTOR; ISOFORMS;
D O I
10.4161/auto.24880
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:1167 / 1171
页数:5
相关论文
共 27 条
[11]   Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8 [J].
Heil, F ;
Hemmi, H ;
Hochrein, H ;
Ampenberger, F ;
Kirschning, C ;
Akira, S ;
Lipford, G ;
Wagner, H ;
Bauer, S .
SCIENCE, 2004, 303 (5663) :1526-1529
[12]   A Toll-like receptor recognizes bacterial DNA [J].
Hemmi, H ;
Takeuchi, O ;
Kawai, T ;
Kaisho, T ;
Sato, S ;
Sanjo, H ;
Matsumoto, M ;
Hoshino, K ;
Wagner, H ;
Takeda, K ;
Akira, S .
NATURE, 2000, 408 (6813) :740-745
[13]   Noncanonical Autophagy Is Required for Type I Interferon Secretion in Response to DNA-Immune Complexes [J].
Henault, Jill ;
Martinez, Jennifer ;
Riggs, Jeffrey M. ;
Tian, Jane ;
Mehta, Payal ;
Clarke, Lorraine ;
Sasai, Miwa ;
Latz, Eicke ;
Brinkmann, Melanie M. ;
Iwasaki, Akiko ;
Coyle, Anthony J. ;
Kolbeck, Roland ;
Green, Douglas R. ;
Sanjuan, Miguel A. .
IMMUNITY, 2012, 37 (06) :986-997
[14]   The Many Pathways of RNA Degradation [J].
Houseley, Jonathan ;
Tollervey, David .
CELL, 2009, 136 (04) :763-776
[15]   Selective autophagy mediated by autophagic adapter proteins [J].
Johansen, Terje ;
Lamark, Trond .
AUTOPHAGY, 2011, 7 (03) :279-296
[16]   Aberrant interaction between Parkinson disease-associated mutant UCH-L1 and the lysosomal receptor for chaperone-mediated autophagy [J].
Kabuta, Tomohiro ;
Furuta, Akiko ;
Aoki, Shunsuke ;
Furuta, Koh ;
Wada, Keiji .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (35) :23731-23738
[17]   Mature ribosomes are selectively degraded upon starvation by an autophagy pathway requiring the Ubp3p/Bre5p ubiquitin protease [J].
Kraft, Claudine ;
Deplazes, Anna ;
Sohrmann, Marc ;
Peter, Matthias .
NATURE CELL BIOLOGY, 2008, 10 (05) :602-610
[18]   Autophagy: Renovation of Cells and Tissues [J].
Mizushima, Noboru ;
Komatsu, Masaaki .
CELL, 2011, 147 (04) :728-741
[19]   Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome [J].
Nakahira, Kiichi ;
Haspel, Jeffrey Adam ;
Rathinam, Vijay A. K. ;
Lee, Seon-Jin ;
Dolinay, Tamas ;
Lam, Hilaire C. ;
Englert, Joshua A. ;
Rabinovitch, Marlene ;
Cernadas, Manuela ;
Kim, Hong Pyo ;
Fitzgerald, Katherine A. ;
Ryter, Stefan W. ;
Choi, Augustine M. K. .
NATURE IMMUNOLOGY, 2011, 12 (03) :222-U57
[20]  
Novikoff AB, 1956, J BIOPHYS BIOCH S179, V2, P84, DOI 10.1083/jcb.2.4.17913357540