Abstract
SIGNIFICANCE: All cellular metabolic processes are tied to the cellular redox environment. Therefore, maintaining redox homeostasis is critically important for normal cell function. Indeed, redox stress contributes to the pathobiology of many human diseases. The cellular redox response system is composed of numerous interconnected components, including free radicals, redox couples, protein thiols, enzymes, metabolites, and transcription factors. Moreover, interactions between and among these factors are regulated in time and space. Owing to their complexity, systems biology approaches to the characterization of the cellular redox response system may provide insights into novel homeostatic mechanisms and methods of therapeutic reprogramming. Recent Advances: The emergence and development of systems biology has brought forth a set of innovative technologies that provide new avenues for studying redox metabolism. This article will review these systems biology approaches and their potential application to the study of redox metabolism in stress and disease states. CRITICAL ISSUES: Clarifying the scope of biological intermediaries affected by dysregulated redox metabolism requires methods that are suitable for analyzing big datasets as classical methods that do not account for multiple interactions are unlikely to portray the totality of perturbed metabolic systems. FUTURE DIRECTIONS: Given the diverse redox microenvironments within cells, it will be important to improve the spatial resolution of omic approaches. Futures studies on the integration of multiple systems-based methods and heterogeneous omics data for redox metabolism are required to accelerate the development of the field of redox systems biology. Antioxid. Redox Signal. 29, 953-972.