Human aquaporin-11 guarantees efficient transport of H2O2 across the endoplasmic reticulum membrane
Stefano Bestetti,
Mauro Galli,
Ilaria Sorrentino,
Paolo Pinton,
Alessandro Rimessi,
Roberto Sitia,
Iria Medraño-Fernandez
Affiliations
Stefano Bestetti
Protein Transport and Secretion Unit, Division of Genetics and Cell Biology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale San Raffaele, Università Vita-Salute San Raffaele, 20132, Milan, Italy
Mauro Galli
Protein Transport and Secretion Unit, Division of Genetics and Cell Biology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale San Raffaele, Università Vita-Salute San Raffaele, 20132, Milan, Italy
Ilaria Sorrentino
Protein Transport and Secretion Unit, Division of Genetics and Cell Biology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale San Raffaele, Università Vita-Salute San Raffaele, 20132, Milan, Italy
Paolo Pinton
Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, 44121, Ferrara, Italy
Alessandro Rimessi
Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, 44121, Ferrara, Italy
Roberto Sitia
Protein Transport and Secretion Unit, Division of Genetics and Cell Biology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale San Raffaele, Università Vita-Salute San Raffaele, 20132, Milan, Italy; Corresponding author.
Iria Medraño-Fernandez
Protein Transport and Secretion Unit, Division of Genetics and Cell Biology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale San Raffaele, Università Vita-Salute San Raffaele, 20132, Milan, Italy; Corresponding author.
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. Keywords: Aquaporins, Peroxiporins, Hydrogen peroxide, Membrane permeability, Endoplasmic reticulum, Redox homeostasis
