| First Author | Ito C | Year | 2013 |
| Journal | Mol Cell | Volume | 52 |
| Issue | 6 | Pages | 794-804 |
| PubMed ID | 24268578 | Mgi Jnum | J:206151 |
| Mgi Id | MGI:5548014 | Doi | 10.1016/j.molcel.2013.10.024 |
| Citation | Ito C, et al. (2013) Endogenous nitrated nucleotide is a key mediator of autophagy and innate defense against bacteria. Mol Cell 52(6):794-804 |
| abstractText | 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). We found 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 selectively marked with polyubiquitin, a known molecular tag for selective transport to autophagosomes. These results collectively indicate that 8-nitro-cGMP plays a crucial role in cytoprotection during bacterial infections or inflammations via autophagy upregulation. |
