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

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