A persulfidation-based mechanism controls aquaporin-8 conductance

Stefano Bestetti, Iria Medraño-Fernandez, Mauro Galli, Michela Ghitti, Gerd P. Bienert, Giovanna Musco, Andrea Orsi, Anna Rubartelli, Roberto Sitia

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

54 Zitate (Scopus)

Abstract

Upon engagement of tyrosine kinase receptors, nicotinamide adenine dinucleotide phosphate (NADPH)-oxidases release H2O2 in the extracellular space.We reported previously that aquaporin-8 (AQP8) transports H2O2 across the plasma membrane and is reversibly gated during cell stress,modulating signal strength and duration.We showthatAQP8 gating ismediated by persulfidation of cysteine 53 (C53). Treatmentwith H2S is sufficient to block H2O2 entry in unstressed cells. Silencing cystathionine b-synthase (CBS) prevents closure, suggesting that this enzyme is the main source of H2S. Molecular modeling indicates that C53 persulfidation displaces a nearby histidine located in the narrowest part of the channel. We propose that H2O2 molecules transported through AQP8 sulfenylate C53, making it susceptible to H2S produced by CBS. This mechanism tunes H2O2 transport and may control signaling and limit oxidative stress.

OriginalspracheEnglisch
Aufsatznummereaar5770
FachzeitschriftScience Advances
Jahrgang4
Ausgabenummer5
DOIs
PublikationsstatusVeröffentlicht - 2 Mai 2018
Extern publiziertJa

Fingerprint

Untersuchen Sie die Forschungsthemen von „A persulfidation-based mechanism controls aquaporin-8 conductance“. Zusammen bilden sie einen einzigartigen Fingerprint.

Dieses zitieren