Vol. 13, Issue 12, 4243-4255, December 2002

Peroxisome Senescence in Human Fibroblasts

Julie E. Legakis,^* Jay I. Koepke,^* Chris Jedeszko, Ferdous Barlaskar,^* Laura J. Terlecky,^* Holly J. Edwards,^* Paul A. Walton, and Stanley R. Terlecky^*

 ^*Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan 48201, and  Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada N6A 5C1

The molecular mechanisms of peroxisome biogenesis have begun to emerge; in contrast, relatively little is known about how the organelle functions as cells age. In this report, we characterize age-related changes in peroxisomes of human cells. We show that aging compromises peroxisomal targeting signal 1 (PTS1) protein import, affecting in particular the critical antioxidant enzyme catalase. The number and appearance of peroxisomes are altered in these cells, and the organelles accumulate the PTS1-import receptor, Pex5p, on their membranes. Concomitantly, cells produce increasing amounts of the toxic metabolite hydrogen peroxide, and we present evidence that this increased load of reactive oxygen species may further reduce peroxisomal protein import and exacerbate the effects of aging.