Absence of the peroxiredoxin Pmp20 causes peroxisomal protein leakage and necrotic cell death.
We analyzed the role of the peroxisomal peroxiredoxin Pmp20 of the yeast Hansenula polymorpha. Cells of a PMP20 disruption strain (pmp20) grew normally on substrates that are not metabolized by peroxisomal enzymes, but showed a severe growth defect on methanol, the metabolism of which involves a hydrogen peroxide producing peroxisomal oxidase. This growth defect was paralleled by leakage of peroxisomal matrix proteins into the cytosol. Methanol-induced pmp20 cells accumulated enhanced levels of reactive oxygen species and lipid peroxidation products. Moreover, the fatty acid composition of methanol-induced pmp20 cells differed relative to WT controls, suggesting an effect on fatty acid homeostasis. Plating assays and FACS-based analysis of cell death markers revealed that pmp20 cells show loss of clonogenic efficiency and membrane integrity, when cultured on methanol. We conclude that the absence of the peroxisomal peroxiredoxin leads to loss of peroxisome membrane integrity and necrotic cell death.
Bener Aksam
Eda
E
Molecular Cell Biology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Haren, The Netherlands.
Jungwirth
Helmut
H
Kohlwein
Sepp D
SD
Ring
Julia
J
Madeo
Frank
F
Veenhuis
Marten
M
van der Klei
Ida J
IJ
D015153:Blotting, Western; D015227:Lipid Peroxidation; D046529:Microscopy, Electron, Transmission; D009336:Necrosis / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D054464:Peroxiredoxins / Q000378:metabolism*; D020675:Peroxisomes / Q000378:metabolism* / Q000648:ultrastructure; D010843:Pichia / Q000502:physiology*; D011506:Proteins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D011506:Proteins; D017382:Reactive Oxygen Species; D054464:Peroxiredoxins