title: Peroxisome senescence in human fibroblasts.
abstract: 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.
authors.affiliation: Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Legakis
authors.forename: Jay I
authors.initials: JI
authors.lastname: Koepke
authors.forename: Chris
authors.initials: C
authors.lastname: Jedeszko
authors.forename: Ferdous
authors.initials: F
authors.lastname: Barlaskar
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Terlecky
authors.forename: Holly J
authors.initials: HJ
authors.lastname: Edwards
authors.forename: Paul A
authors.initials: PA
authors.lastname: Walton
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Terlecky
mesh_terms: D000375:Aging; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D016922:Cellular Senescence; D003902:Detergents / Q000494:pharmacology; D004072:Digitonin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D010450:Endopeptidases / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology*; D049452:Green Fluorescent Proteins; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007150:Immunohistochemistry; D008164:Luminescent Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D017830:Octoxynol / Q000494:pharmacology; D000074435:Peroxisome-Targeting Signal 1 Receptor; D020675:Peroxisomes / Q000473:pathology*; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013997:Time Factors
chemical_list: D003902:Detergents; D008164:Luminescent Proteins; D008565:Membrane Proteins; D000074435:Peroxisome-Targeting Signal 1 Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; C085380:peroxisomal targeting sequence receptor; D049452:Green Fluorescent Proteins; D017830:Octoxynol; D006861:Hydrogen Peroxide; D010450:Endopeptidases; D004072:Digitonin