The discovery of the colocalization of
catalase with H2O2-generating
oxidases in peroxisomes was the first indication of their involvement in the metabolism of
oxygen metabolites. In past decades it has been revealed that peroxisomes participate not only in the generation of
reactive oxygen species (ROS) with grave consequences for cell fate such as malignant degeneration but also in cell rescue from the damaging effects of such radicals. In this review the role of peroxisomes in a variety of physiological and
pathological processes involving ROS mainly in animal cells is presented. At the outset the
enzymes generating and scavenging H2O2 and other
oxygen metabolites are reviewed. The exposure of cultured cells to UV light and different
oxidizing agents induces peroxisome proliferation with formation of tubular peroxisomes and apparent upregulation of PEX genes. Significant reduction of peroxisomal volume density and several of their
enzymes is observed in inflammatory processes such as
infections,
ischemia-reperfusion injury and hepatic allograft rejection. The latter response is related to the suppressive effects of
TNFalpha on peroxisomal function and on
PPARalpha. Their massive proliferation induced by a variety of
xenobiotics and the subsequent
tumor formation in rodents is evidently due to an imbalance in the formation and scavenging of ROS, and is mediated by
PPARalpha. In PEX5-/- mice with the absence of functional peroxisomes severe abnormalities of mitochondria in different organs are observed which resemble closely those in respiratory chain disorders associated with oxidative stress. Interestingly, no evidence of oxidative damage to
proteins or
lipids, nor of increased
peroxide production has been found in that mouse model. In this respect the role of
PPARalpha, which is highly activated in those mice, in prevention of oxidative stress deserves further investigation.