Redox Signaling from and to Peroxisomes: Progress, Challenges, and Prospects

Significance: Peroxisomes are organelles that are best known for their role in cellular lipid and hydrogen peroxide (H2O2) metabolism. Emerging evidence suggests that these organelles serve as guardians and modulators of cellular redox balance, and that alterations in their redox metabolism may contribute to aging and the development of chronic diseases such as neurodegeneration, diabetes, and cancer. Recent Advances: H2O2 is an important signaling messenger that controls many cellular processes by modulating protein activity through cysteine oxidation. Somewhat surprisingly, the potential involvement of peroxisomes in H2O2-mediated signaling processes has been overlooked for a long time. However, recent advances in the development of live-cell approaches to monitor and modulate spatiotemporal fluxes in redox species at the subcellular level have opened up new avenues for research in redox biology and boosted interest in the concept of peroxisomes as redox signaling platforms. Critical Issues: This review first introduces the reader to what is known about the role of peroxisomes in cellular H2O2 production and clearance, with a focus on mammalian cells. Next, it briefly describes the benefits and drawbacks of current strategies used to investigate the complex interplay between peroxisome metabolism and cellular redox state. Furthermore, it integrates and critically evaluates literature dealing with the interrelationship between peroxisomal redox metabolism, cell signaling, and human disease. Future Directions: As the precise molecular mechanisms underlying many of these associations are still poorly understood, a key focus for future research should be the identification of primary targets for peroxisome-derived H2O2.