Peroxisomes and aging

Abstract

Peroxisomes are indispensable for proper functioning of human cells. They efficiently compartmentalize enzymes responsible for a number of metabolic processes, including the absolutely essential beta-oxidation of specific fatty acid chains. These and other oxidative reactions produce hydrogen peroxide, which is, in most instances, immediately processed in situ to water and oxygen. The responsible peroxidase is the heme-containing tetrameric enzyme, catalase. What has emerged in recent years is that there are circumstances in which the tightly regulated balance of hydrogen peroxide producing and degrading activities in peroxisomes is upset-leading to the net production and accumulation of hydrogen peroxide and downstream reactive oxygen species. The factor most essentially involved is catalase, which is missorted in aging, missing or present at reduced levels in certain disease states, and inactivated in response to exposure to specific xenobiotics. The overall goal of this review is to summarize the molecular events associated with the development and advancement of peroxisomal hypocatalasemia and to describe its effects on cells. In addition, results of recent efforts to increase levels of peroxisomal catalase and restore oxidative balance in cells will be discussed.

DyP-type peroxidases comprise a novel heme peroxidase family

“…In contrast to plant peroxidases, most enzymes isolated from mammals and other animals have not yet been classified. However, several animal peroxidases have been studied with regards to roles in disease and aging [13][14][15]. Recently, evolutionary relationships among mammalian heme peroxidases have been proposed by advanced phylogenetic analysis [16].…”

Redox compartmentalization in eukaryotic cells

“…Inhibition and mislocation of catalase resulted in multiple peroxisomal enzymatic dysfunctions and deficiencies [183,184]. Deficiency of peroxisomal catalase caused developmental abnormalities while its overexpression in transgenic mice resulted in extended life span suggesting that catalase in peroxisomes has an important role in cell survival and aging mechanisms [185].…”

Ubp15p, a Ubiquitin Hydrolase Associated with the Peroxisomal Export Machinery

“…Slowing of Pex5p cycling is most certainly associated with reduced import rates. Interestingly, induction of oxidative stress by treating cells with hydrogen peroxide causes Pex5p to amass on the organelle membrane and significantly reduces PTS1 protein import (73)(74)(75). As our data are clear in that Ubp15p can deubiquitinate Pex5p and as the ubiquitination status of the PTS1 receptor directly influences its cycling (10,11), it is conceivable that the deletion of Ubp15p influences the import process of PTS1 proteins like catalase and thus possibly also morphology and clustering of peroxisomes.…”