@article{83ad34b7e22048bc9c8475c565ee41af,
title = "Endogenous nitrated nucleotide is a key mediator of autophagy and innate defense against bacteria",
abstract = "Autophagy is a cellular self-catabolic process wherein organelles, macromolecules, and invading microbes are sequestered in autophagosomes that fuse with lysosomes. In this study, we uncover the role of nitric oxide (NO) as a signaling molecule for autophagy induction via its downstream mediator, 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP). Wefound that 8-nitro-cGMP-induced autophagy is mediated by Lys63-linked polyubiquitination and that endogenous 8-nitro-cGMP promotes autophagic exclusion of invading group A Streptococcus (GAS) from cells. 8-nitro-cGMP can modify Cys residues by S-guanylation of proteins. We showed that intracellular GAS is modified with S-guanylation extensively in autophagosomes-like vacuoles, suggesting the role of S-guanylation as a marker for selective autophagic degradation. This finding is supported by the fact that S-guanylated bacteria were selectivelymarked with polyubiquitin, a known molecular tag forselective transport to autophagosomes. Theseresults collectively indicate that 8-nitro-cGMPplays acrucial role in cytoprotection during bacterialinfections or inflammations via autophagy upregulation.",
author = "Chiaki Ito and Yohei Saito and Takashi Nozawa and Shigemoto Fujii and Tomohiro Sawa and Hirofumi Inoue and Tetsuro Matsunaga and Shahzada Khan and Soichiro Akashi and Ryota Hashimoto and Chihiro Aikawa and Eriko Takahashi and Hiroshi Sagara and Masaaki Komatsu and Keiji Tanaka and Takaaki Akaike and Ichiro Nakagawa and Hirokazu Arimoto",
note = "Funding Information: We thank Drs. N. Nukina and G. Matsumoto (RIKEN) for providing the plasmids expressing ubiquitins; Dr. N. Mizushima (University of Tokyo) for providing us with Atg5 −/− MEF cells and Hela cells stably expressing EGFP-LC3; and Dr. Takashi Maruyama (Tohoku University), Dr. T. Okamoto (Kumamoto University), and Dr. A. Higashitani (Tohoku University) for their technical assistance. We also wish to thank the late Dr. T. Muta (Tohoku University) for his encouragement and constructive discussions. This work was supported in part by grants-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan (20117006, 21310136, 25282236 to H.A.; 21006401 to Y.S.; 246857 to C.I.); the Uehara Memorial Foundation (to H.A.); and the Funding Program for NEXT Generation World-Leading Researchers (NEXT) Program LC041 (to T.N. and I.N.). C.I. wishes to thank JSPS and the Suntory Foundation for Life Sciences for Research Fellowships. ",
year = "2013",
month = dec,
day = "26",
doi = "10.1016/j.molcel.2013.10.024",
language = "English",
volume = "52",
pages = "794--804",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "6",
}