1. Academic Validation
  2. Human aquaporin-11 guarantees efficient transport of H2O2 across the endoplasmic reticulum membrane

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

  • Redox Biol. 2020 Jan;28:101326. doi: 10.1016/j.redox.2019.101326.
Stefano Bestetti 1 Mauro Galli 1 Ilaria Sorrentino 1 Paolo Pinton 2 Alessandro Rimessi 2 Roberto Sitia 3 Iria Medraño-Fernandez 4
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 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. Electronic address: [email protected].
  • 4 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. Electronic address: [email protected].
Abstract

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; Endoplasmic reticulum; Hydrogen peroxide; Membrane permeability; Peroxiporins; Redox homeostasis.

Figures