Compartment-dependent management of H(2)O(2) by peroxisomes.
Peroxisomes (PO) are essential and ubiquitous single-membrane-bound organelles whose ultrastructure is characterized by a matrix and often a crystalloid core. A unique feature is their capacity to generate and degrade H(2)O(2) via several oxidases and catalase, respectively. Handling of H(2)O(2) within PO is poorly understood and, in contrast to mitochondria, they are not regarded as a default H(2)O(2) source. Using an ultrasensitive luminometric H(2)O(2) assay, we show in real time that H(2)O(2) handling by matrix-localized catalase depends on the localization of H(2)O(2) generation in- and outside the PO. Thus, intact PO are inefficient at degrading external but also internal H(2)O(2) that is generated by the core-localized urate oxidase (UOX). Our findings suggest that, in addition to the PO membrane, the matrix forms a significant diffusion barrier for H(2)O(2). In contrast, matrix-generated H(2)O(2) is efficiently degraded. We further show that the tubular structures in crystalloid cores of UOX are associated with and perpendicularly oriented toward the PO membrane. Studies on metabolically active liver slices demonstrate that UOX directly releases H(2)O(2) into the cytoplasm, with the 5-nm primary tubules in crystalloid cores serving as exhaust conduits. Apparently, PO are inefficient detoxifiers of external H(2)O(2) but rather can become an obligatory source of H(2)O(2)--an important signaling molecule and a potential toxin.
Fritz
Reiner
R
Department of Internal Medicine, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
Bol
Jutta
J
Hebling
Ulrike
U
Angermüller
Sabine
S
Völkl
Alfred
A
Fahimi
H Dariush
HD
Mueller
Sebastian
S
D015153:Blotting, Western; D002374:Catalase / Q000378:metabolism; D002451:Cell Compartmentation; D002850:Chromatography, Gel; D004591:Electrophoresis, Polyacrylamide Gel; D006861:Hydrogen Peroxide / Q000378:metabolism*; D020675:Peroxisomes / Q000378:metabolism*; D015398:Signal Transduction
D006861:Hydrogen Peroxide; D002374:Catalase