State Key Laboratory of Plant Genomics and CAS Center for Excellence in Molecular Plant Sciences, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
State Key Laboratory of Plant Genomics and CAS Center for Excellence in Molecular Plant Sciences, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; State Key Laboratory of Rice Biology, China National Rice Research Institute, Chinese Academy of Agricultural Sciences, Hangzhou 310006, China.
Mol Cell. 2018 Jul 5;71(1):142-154.e6. doi: 10.1016/j.molcel.2018.05.024. Epub 2018 Jun 28.
Nitric oxide (NO) regulates diverse cellular signaling through S-nitrosylation of specific Cys residues of target proteins. The intracellular level of S-nitrosoglutathione (GSNO), a major bioactive NO species, is regulated by GSNO reductase (GSNOR), a highly conserved master regulator of NO signaling. However, little is known about how the activity of GSNOR is regulated. Here, we show that S-nitrosylation induces selective autophagy of Arabidopsis GSNOR1 during hypoxia responses. S-nitrosylation of GSNOR1 at Cys-10 induces conformational changes, exposing its AUTOPHAGY-RELATED8 (ATG8)-interacting motif (AIM) accessible by autophagy machinery. Upon binding by ATG8, GSNOR1 is recruited into the autophagosome and degraded in an AIM-dependent manner. Physiologically, the S-nitrosylation-induced selective autophagy of GSNOR1 is relevant to hypoxia responses. Our discovery reveals a unique mechanism by which S-nitrosylation mediates selective autophagy of GSNOR1, thereby establishing a molecular link between NO signaling and autophagy.
一氧化氮（NO）通过靶蛋白特定半胱氨酸残基的 S-亚硝基化来调节多种细胞信号转导。S-亚硝基谷胱甘肽（GSNO）是一种主要的生物活性 NO 物质，其细胞内水平受 GSNO 还原酶（GSNOR）调节，GSNOR 是 NO 信号的高度保守的主调控因子。然而，关于 GSNOR 的活性如何调节，人们知之甚少。在这里，我们表明，在缺氧反应中，S-亚硝基化诱导拟南芥 GSNOR1 的选择性自噬。GSNOR1 的 Cys-10 上的 S-亚硝基化诱导构象变化，暴露出其可被自噬机制结合的 ATG8 相互作用基序（AIM）。与 ATG8 结合后，GSNOR1 被招募到自噬体中，并以 AIM 依赖性方式降解。从生理上讲，GSNOR1 的 S-亚硝基化诱导的选择性自噬与缺氧反应有关。我们的发现揭示了 S-亚硝基化介导 GSNOR1 选择性自噬的独特机制，从而在 NO 信号和自噬之间建立了分子联系。
