Endogenous nitrated nucleotide is a key mediator of autophagy and innate defense against bacteria

Chiaki Ito, Yohei Saito, Takashi Nozawa, Shigemoto Fujii, Tomohiro Sawa, Hirofumi Inoue, Tetsuro Matsunaga, Shahzada Khan, Soichiro Akashi, Ryota Hashimoto, Chihiro Aikawa, Eriko Takahashi, Hiroshi Sagara, Masaaki Komatsu, Keiji Tanaka, Takaaki Akaike, Ichiro Nakagawa, Hirokazu Arimoto

研究成果: Article査読

63 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)794-804
ページ数11
ジャーナルMolecular Cell
52
6
DOI
出版ステータスPublished - 2013 12 26

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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