Anaerobic Transcription by OxyR: A Novel Paradigm for Nitrosative Stress.

Published

Journal Article

Significance: S-nitrosylation, the post-translational modification by nitric oxide (NO) to form S-nitrosothiols (SNOs), regulates diverse aspects of cellular function, and aberrant S-nitrosylation (nitrosative stress) is implicated in disease, from neurodegeneration to cancer. Essential roles for S-nitrosylation have been demonstrated in microbes, plants, and animals; notably, bacteria have often served as model systems for elucidation of general principles. Recent Advances: Recent conceptual advances include the idea of a molecular code through which proteins sense and differentiate S-nitrosothiol (SNO) from alternative oxidative modifications, providing the basis for specificity in SNO signaling. In Escherichia coli, S-nitrosylation relies on an enzymatic cascade that regulates, and is regulated by, the transcription factor OxyR under anaerobic conditions. S-nitrosylated OxyR activates an anaerobic regulon of >100 genes that encode for enzymes that both mediate S-nitrosylation and protect against nitrosative stress. Critical Issues: Mitochondria originated from endosymbiotic bacteria and generate NO under hypoxic conditions, analogous to conditions in E. coli. Nitrosative stress in mitochondria has been implicated in Alzheimer's and Parkinson's disease, among others. Many proteins that are S-nitrosylated in mitochondria are also S-nitrosylated in E. coli. Insights into enzymatic regulation of S-nitrosylation in E. coli may inform the identification of disease-relevant regulatory machinery in mammalian systems. Future Directions: Using E. coli as a model system, in-depth analysis of the anaerobic response controlled by OxyR may lead to the identification of enzymatic mechanisms regulating S-nitrosylation in particular, and hypoxic signaling more generally, providing novel insights into analogous mechanisms in mammalian cells and within dysfunctional mitochondria that characterize neurodegenerative diseases.

Full Text

Duke Authors

Cited Authors

  • Seth, D; Hausladen, A; Stamler, JS

Published Date

  • April 20, 2020

Published In

Volume / Issue

  • 32 / 12

Start / End Page

  • 803 - 816

PubMed ID

  • 31691575

Pubmed Central ID

  • 31691575

Electronic International Standard Serial Number (EISSN)

  • 1557-7716

Digital Object Identifier (DOI)

  • 10.1089/ars.2019.7921

Language

  • eng

Conference Location

  • United States