Lack of Peroxisomal Catalase Causes a Progeric Phenotype in Caenorhabditis elegans

Abstract

Studies using the nematode Caenorhabditis elegans as a model system to investigate the aging process have implicated the insulin/insulin-like growth factor-I signaling pathway in the regulation of organismal longevity through its action on a subset of target genes. These targets can be classified into genes that shorten or extend life-span upon their induction. Genes that shorten life-span include a variety of stress response genes, among them genes encoding catalases; however, no evidence directly implicates catalases in the aging process of nematodes or other organisms. Using genetic mutants, we show that lack of peroxisomal catalase CTL-2 causes a progeric phenotype in C. elegans. Lack of peroxisomal catalase also affects the developmental program of C. elegans, since ⌬ctl-2 mutants exhibit decreased egg laying capacity. In contrast, lack of cytosolic catalase CTL-1 has no effect on either nematode aging or egg laying capacity. The ⌬ctl-2 mutation also shortens the maximum life-span of the long lived ⌬clk-1 mutant and accelerates the onset of its egg laying period. The more rapid aging of ⌬ctl-2 worms is apparently not due to increased carbonylation of the major C. elegans proteins, although altered peroxisome morphology in the ⌬ctl-2 mutant suggests that changes in peroxisomal function, including increased production of reactive oxygen species, underlie the progeric phenotype of the ⌬ctl-2 mutant. Our findings support an important role for peroxisomal catalase in both the development and aging of C. elegans and suggest the utility of the ⌬ctl-2 mutant as a convenient model for the study of aging and the human diseases acatalasemia and hypocatalasemia.

Lack of heme synthesis in a free-living eukaryote

“…elegans appears to have a large number of hemoprotein orthologs, including globin isoforms (26), guanylate cyclases (27), adenylate cyclases (28), catalases (29), cytochrome P450s (30), and respiratory cytochromes (31). Although hemes have been found in all phyla, certain microbial pathogens such as Borrelia burgdorferi and Treponema pallidum neither make heme nor contain hemoproteins (19,32).…”

Oxidative Stress Enzymes Are Required for DAF-16-Mediated Immunity Due to Generation of Reactive Oxygen Species byCaenorhabditis elegans

“…elegans strains and growth conditions: C. elegans strains were grown and maintained as previously described (Hope 1999). All C. elegans strains used were obtained from the Caenorhabditis Genetics Center except for ctl-1(u800)II and ctl-2(ua90)II, which were obtained from R. Rachubinski (Petriv and Rachubinski 2004). sod-3(gk235)X is a deletion mutant created by the C. elegans Reverse Genetics Core Facility at the University of British Columbia, part of the International C. elegans Gene Knockout Consortium.…”

“…(A) N2 and ctl-1(u800)II (Petriv and Rachubinski 2004). (B) N2 and ctl-2(ua90)II (Petriv and Rachubinski 2004). (C) N2 and sod-3 (gk235)X.…”

“…Two asterisks indicate a significant difference (P , 0.05) compared to N2 worms exposed to daf-2 RNAi. this might be due to a general decrease in fitness since ctl-2 has been characterized as having a slightly shorter life span (Petriv and Rachubinski 2004). Therefore, longevity assays (Table 1) were performed on all the strains and RNAi conditions shown in Figure 6D and the relative mortality calculated in Figure 6E.…”

Role of Intracellular Hydrogen Peroxide as Signalling Molecule for Plant Senescence

“…The loss of such an important enzyme has to be compensated somehow during development but it would be expected that these knock-out plants are more sensitive against all stresses implying an increased ROS production and that they most likely show a senescence phenotype. The lack of peroxisomal catalase CTL-2 in Caenorhabditis elegans causes a progeric phenotype whereas the lack of the cytosolic catalase CTL-1 has no effect on nematode aging (Petriv & Rachubinski, 2004). In yeast, catalase T activity but not catalase A activity was necessary to assure longevity under repressing conditions on glucose media.…”