Abstract
Hydrogen peroxide (H2O2), 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 H2O2 signaling network. We first briefly introduce the basic concepts of how H2O2 can drive cellular signaling events. Next, we outline the peroxisomal enzyme systems involved in H2O2 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 H2O2 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 H2O2 signaling network is of key importance to unravel the precise role of peroxisomal H2O2 production and scavenging in normal and pathological conditions.
Highlights
Hydrogen peroxide (H2O2), the non-radical 2-electron reduction product of oxygen, is a natural metabolite commonly found in aerobic organisms [1]
Whether H2O2 acts as a signaling molecule or leads to oxidative damage of biomolecules, a condition denoted as oxidative stress, depends on the cellular context, its local concentration, and the kinetics of its production and elimination [4]
May display a dual function: on one hand, they can function as H2O2 scavengers that counteract redox signaling; on the other hand, they may act as enablers of protein thiol oxidation by transferring oxidative equivalents from H2O2 to redox-regulated proteins [34]
Summary
Hydrogen peroxide (H2O2), the non-radical 2-electron reduction product of oxygen, is a natural metabolite commonly found in aerobic organisms [1]. Other metabolic functions of peroxisomes in mammals include glyoxylate detoxification, amino acid catabolism, polyamine oxidation, and the production and scavenging of reactive oxygen and nitrogen species (ROS and RNS, respectively) [16,17]. These organelles are increasingly recognized as important hubs in innate immune-, lipid-, inflammatory-, and redox-signaling networks [18]. To perform these functions, peroxisomes can dynamically regulate their number, shape, and protein content in response to changing environmental conditions [19]. We focus on the role of mammalian peroxisomes in cellular H2O2 metabolism and how perturbations in this process may affect cellular function and organismal health
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