Significance: S-nitrosylation (SNO) has been identified throughout the body as an important signaling modification both in physiology and a variety of diseases. SNO is a multifaceted post-translational modification, in that it can either act as a signaling molecule itself or as an intermediate to other modifications.
Recent advances and critical issues: Through extensive SNO research, we have made progress toward understanding the importance of single cysteine-SNO sites; however, we are just beginning to explore the importance of specific SNO within the context of other SNO sites and post-translational modifications. Additionally, compartmentalization and SNO occupancy may play an important role in the consequences of the SNO modification.
Future directions: In this review, we will consider the context of SNO signaling and discuss how the transient nature of SNO, its role as an oxidative intermediate, and the pattern of SNO, should be considered when determining the impact of SNO signaling.