Cited by 110Redox biology and oxidative stressGenetics, Aging, and Longevity in Model OrganismsAutophagy in Disease and Therapy

Restoration of Peroxisomal Catalase Import in a Model of Human Cellular Aging

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Koepke, Jay I., Nakrieko, Kerry‐Ann, Wood, Christopher S., Boucher, Krissy K., Terlecky, Laura J., Walton, Paul A., Terlecky, Stanley R.·2007·Traffic

Abstract

Peroxisomes play an important role in human cellular metabolism by housing enzymes involved in a number of essential biochemical pathways. Many of these enzymes are oxidases that transfer hydrogen atoms to molecular oxygen forming hydrogen peroxide. The organelle also contains catalase, which readily decomposes the hydrogen peroxide, a potentially damaging oxidant. Previous work has demonstrated that aging compromises peroxisomal protein import with catalase being particularly affected. The resultant imbalance in the relative ratio of oxidases to catalase was seen as a potential contributor to cellular oxidative stress and aging. Here we report that altering the peroxisomal targeting signal of catalase to the more effective serine‐lysine‐leucine (SKL) sequence results in a catalase molecule that more strongly interacts with its receptor and is more efficiently imported in both in vitro and in vivo assays. Furthermore, catalase‐SKL monomers expressed in cells interact with endogenous catalase subunits resulting in altered trafficking of the latter molecules. A dramatic reduction in cellular hydrogen peroxide levels accompanies this increased peroxisomal import of catalase. Finally, we show that catalase‐SKL stably expressed in cells by retroviral‐mediated transduction repolarizes mitochondria and reduces the number of senescent cells in a population. These results demonstrate the utility of a catalase‐SKL therapy for the restoration of a normal oxidative state in aging cells.

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Authors
Koepke, J. I., Nakrieko, K., Wood, C. S., Boucher, K. K., Terlecky, L. J., Walton, P. A., & Terlecky, S. R.
Affiliations
  • Wayne State University (US)
  • Western University (CA)
Corresponding author
Terlecky, Stanley R.
Venue
Traffic
Publisher
Wiley
Published
2007-08-07
Volume
8
Issue
11
Pages
1590-1600
ISSN
  • 1398-9219 (ISSN-L)
  • 1600-0854
OpenAlex
W1970748148
Cited by
110
References
41
Citations by year
2026: 2 · 2025: 4 · 2024: 5 · 2023: 4 · 2022: 5 · 2021: 7 · 2020: 8 · 2019: 1 · 2018: 5 · 2017: 8 · 2016: 4 · 2015: 5 · 2014: 6 · 2013: 10 · 2012: 12
FWCI
2.25
Type
journal article
Language
en
Open access
Locations
  • Traffic (publishedVersion, public-domain)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5p30es006639-15, ES06639, P30 ES06639)
  • Canadian Institutes of Health Research
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK056299, DK-56299)
  • National Institute of Environmental Health Sciences (P-30-ES06639, ES06639)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
catalase, peroxisomal protein import, peroxisome biogenesis, cellular aging, peroxisomal targeting signal, hydrogen peroxide, oxidative stress, cellular senescence, retroviral transduction
MeSH terms
Animals, Biochemistry, Catalase, Cricetulus, Fibroblasts, Cricetinae, Humans, Oxidoreductases, Time Factors, Signal Transduction, CHO Cells, Cellular Senescence, Reactive Oxygen Species, Surface Plasmon Resonance, Peroxisomes, Cell Line, Tumor

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