Role of peroxisomes in ROS/RNS-metabolism: Implications for human disease

Abstract

Peroxisomes are cell organelles that play a central role in lipid metabolism. At the same time, these organelles generate reactive oxygen and nitrogen species as byproducts. Peroxisomes also possess intricate protective mechanisms to counteract oxidative stress and maintain redox balance. An imbalance between peroxisomal reactive oxygen species/reactive nitrogen species production and removal may possibly damage biomolecules, perturb cellular thiol levels, and deregulate cellular signaling pathways implicated in a variety of human diseases. Somewhat surprisingly, the potential role of peroxisomes in cellular redox metabolism has been underestimated for a long time. However, in recent years, peroxisomal reactive oxygen species/reactive nitrogen species metabolism and signaling have become the focus of a rapidly evolving and multidisciplinary research field with great prospects. This review is mainly devoted to discuss evidence supporting the notion that peroxisomal metabolism and oxidative stress are intimately interconnected and associated with age-related diseases. We focus on several key aspects of how peroxisomes contribute to cellular reactive oxygen species/reactive nitrogen species levels in mammalian cells and how these cells cope with peroxisome-derived oxidative stress. We also provide a brief overview of recent strategies that have been successfully employed to detect and modulate the peroxisomal redox status. Finally, we highlight some gaps in our knowledge and propose potential avenues for further research. This article is part of a Special Issue entitled: Metabolic Functions and Biogenesis of peroxisomes in Health and Disease.

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“…Furthermore, NO can modulate mitochondrial biogenesis through its ability to regulate ROS production and mitochondrial O 2 consumption (217,254,360). Besides mitochondria, RNS can be generated in mammalian cells by peroxisomes (94) or the plasma membrane. It has been proposed that endogenous hydrogen sulfide (H 2 S), a naturally occurring gassotransmitter similar to NO, plays a particularly important role in the process of acute O 2 sensing in blood vessels (224) and the mammalian carotid body (225).…”

The role of the antioxidant system during intense endurance exercise: lessons from migrating birds

“…The third group of antioxidant enzymes, CAT, is completely located in the peroxisome (Fransen et al, 2012;Halliwell and Gutteridge, 2007;Martensson et al, 1990;Scott et al, 1969). CAT cannot remove any H 2 O 2 produced in the mitochondria unless the RS diffuses from the mitochondria to peroxisomes (Halliwell and Gutteridge, 2007).…”

Toxicological Risk Assessment of Emerging Nanomaterials: Cytotoxicity, Cellular Uptake, Effects on Biogenesis and Cell Organelle Activity, Acute Toxicity and Biodistribution of Oxide Nanoparticles

“…Their dysfunctions can lead to serious consequences. For instance, mitochondrial alterations can go as far as to activate apoptosis [48], peroxisomal dysfunction affect the mitochondria, subsequently leading to oxidative stress and cell death [49,50], alterations of the lysosome may have consequences on the induction of autophagy and apoptosis [51], endoplasmic reticulum damages can lead to reticulum stress which can trigger different forms of cell death in extreme cases [52], and Golgi apparatus dysfunctions can disturb post-translational modifications and vesicular transport [53]. The incidence of the cytotoxicity of nanoparticles is often addressed in generalized terms such as induction of cell death, oxidative stress stimulation, inflammation activation and genotoxicity.…”