A persulfidation-based mechanism controls aquaporin-8 conductance

S Bestetti, I Medraño-Fernandez, M Galli, M Ghitti, GP Bienert, G Musco, A Orsi, A Rubartelli, R Sitia

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Upon engagement of tyrosine kinase receptors, nicotinamide adenine dinucleotide phosphate (NADPH)-oxidases release H2O2in the extracellular space.We reported previously that aquaporin-8 (AQP8) transports H2O2across 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 H2O2entry 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 H2O2molecules transported through AQP8 sulfenylate C53, making it susceptible to H2S produced by CBS. This mechanism tunes H2O2transport and may control signaling and limit oxidative stress. © 2018 The Authors.
Original languageEnglish
Article numbereaar5770
JournalScience advances
Issue number5
Publication statusPublished - 2018


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