Compartment-dependent management of H2O2 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 H2O2 via several oxidases and catalase, respectively. Handling of H2O2 within PO is poorly understood and, in contrast to mitochondria, they are not regarded as a default H2O2 source. Using an ultrasensitive luminometric H2O2 assay, we show in real time that H2O2 handling by matrix-localized catalase depends on the localization of H2O2 generation in- and outside the PO. Thus, intact PO are inefficient at degrading external but also internal H2O2 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 H2O2. In contrast, matrix-generated H2O2 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 H2O2 into the cytoplasm, with the 5-nm primary tubules in crystalloid cores serving as exhaust conduits. Apparently, PO are inefficient detoxifiers of external H2O2 but rather can become an obligatory source of H2O2—an important signaling molecule and a potential toxin.