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. Mol. Cell. (2013) 52(6):794-804.

Speaker: Po-Sheng Tsai (蔡伯昇)                  Time: 14:00~15:00, June. 11, 2014

Commentator: Dr. Pei-Jane Tsai (蔡佩珍老師)                        Place: Room 5761

Abstract

Autophagy is a cellular process which can degrade redundant proteins and organelles. It is also known as the innate defense against invading microbes, including group A Streptococcus (GAS) (1). Previous studies reported that lipopolysaccharide-mediated autophagy in cardiomyocytes depends on both reactive oxygen species and nitric oxide (2). However, the role of reactive nitrogen species in activation of autophagy is still not well studied. The authors have reported that lipopolysaccharide and interferon-γ stimulation of cells trigger the generation of reactive nitrogen species and 8-nitroguanosine 3’, 5’-cyclic monophosphate (8-nitro-cGMP) (3). In this study, the authors demonstrated that 8-nitro-cGMP enhanced the induction of autophagy in macrophages. Furthermore, the Lys63-linked polyubiquitination was triggered by S-guanylated surface of GAS and induced selective autophagy. The 8-nitro-cGMP-enhanced autophagy increased the clearance of intracellular GAS by the S-guanylation of bacterial surface proteins. To identify the S-guanylation targets on GAS surface, the authors extracted and analyzed the S-guanylation-positive proteins such as GAPDH and fructose-bisphosphate aldolase. In conclusion, the authors found that the nitrated mediator, 8-nitro-cGMP S-guanylated the surface protein of GAS and triggered the Lys63-linked polyubiquitination to induce selective autophagy as a defense against invading bacteria.

References:

1.     Nakagawa I, Amano A, Mizushima N, Yamamoto A et al. (2004). Autophagy defends cells against invading group A Streptococcus. Science. 306, 1037–1040.

2.     Yuan H, Perry CN, Huang C, Iwai-Kanai E, Carreira RS, Glembotski CC et al. (2009). LPS-induced autophagy is mediated by oxidative signaling in cardiomyocytes and is associated withcytoprotection. Am. J. Physiol. Heart Circ. Physiol. 296, H470–H479.

3.     Sawa T, Zaki MH, Okamoto T, Akuta T, Tokutomi Y, Fujii S et al. (2007). Protein S-guanylation by the biological signal 8-nitroguanosine 30,50-cyclic monophosphate. Nat. Chem. Biol. 3, 727–735.