Human aquaporin-11 guarantees efficient transport of H2O2 across the endoplasmic reticulum membrane

Hydrogen peroxide (H₂O₂) is an essential second intracellular messenger. To reach its targets in the cytosol, H₂O₂ must cross a membrane, a feat that requires aquaporins (AQP) endowed with 'peroxiporin' activity (AQP3, AQP8, AQP9). Here, we exploit different organelle-targeted H₂O₂-sensitive probes to show that also AQP11 efficiently conduits H₂O₂. Unlike Other peroxiporins, AQP11 is localized in the endoplasmic reticulum (ER), accumulating partly in mitochondrial-associated ER membranes (MAM). Its downregulation severely perturbs the flux of H₂O₂ through the ER, but not through the mitochondrial or plasma membranes. These properties make AQP11 a potential regulator of ER redox homeostasis and signaling.