Peroxisome senescence in human fibroblasts.
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.
Legakis
Julie E
JE
Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Koepke
Jay I
JI
Jedeszko
Chris
C
Barlaskar
Ferdous
F
Terlecky
Laura J
LJ
Edwards
Holly J
HJ
Walton
Paul A
PA
Terlecky
Stanley R
SR
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
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