ABSTRACT
As befits their name, peroxisomes play a central role in cellular hydrogen peroxide (H2O2) metabolism. In addition, it is increasingly appreciated that changes in peroxisomal H2O2 metabolism can actively contribute to the initiation and progression of redox stress-related human pathologies such as cancer, diabetes, and neurodegeneration. However, to function as a subcellular hub for H2O2 metabolism and signaling, peroxisomes must exchange this oxidant with their environment. After providing some basic background information on the concepts and importance of reduction-oxidation (redox) regulation in living cells, this chapter introduces the reader to what is known about peroxisomal H2O2 metabolism and signaling, with a focus on human health and disease. In addition, it reviews research carried out to better understand how H2O2 permeates the peroxisomal membrane. Furthermore, it examines the human peroxisomal membrane proteome in search of proteins with peroxiporin-like properties, thereby focusing on the long-standing question if we already hold the key to unlocking this yet unsolved mystery. Finally, the chapter concludes with a brief reflection on potential research directions in this fascinating but challenging field.
