| Summary: | Hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), a non-radical reactive oxygen species generated during many (patho)physiological conditions, is currently universally recognized as an important mediator of redox-regulated processes. Depending on its spatiotemporal accumulation profile, this molecule may act as a signaling messenger or cause oxidative damage. The focus of this review is to comprehensively evaluate the evidence that peroxisomes, organelles best known for their role in cellular lipid metabolism, also serve as hubs in the H<sub>2</sub>O<sub>2</sub> signaling network. We first briefly introduce the basic concepts of how H<sub>2</sub>O<sub>2</sub> can drive cellular signaling events. Next, we outline the peroxisomal enzyme systems involved in H<sub>2</sub>O<sub>2</sub> metabolism in mammals and reflect on how this oxidant can permeate across the organellar membrane. In addition, we provide an up-to-date overview of molecular targets and biological processes that can be affected by changes in peroxisomal H<sub>2</sub>O<sub>2</sub> metabolism. Where possible, emphasis is placed on the molecular mechanisms and factors involved. From the data presented, it is clear that there are still numerous gaps in our knowledge. Therefore, gaining more insight into how peroxisomes are integrated in the cellular H<sub>2</sub>O<sub>2</sub> signaling network is of key importance to unravel the precise role of peroxisomal H<sub>2</sub>O<sub>2</sub> production and scavenging in normal and pathological conditions.
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