RT Journal Article
T1 A persulfidation-based mechanism controls aquaporin-8 conductance
A1 Bestetti, Stefano
A1 Medraño Fernandez, Iria
A1 Galli, Mauro
A1 Ghitti, Michela
A1 Bienert, Gerd P.
A1 Musco, Giovanna
A1 Orsi, Andrea
A1 Rubartelli, Anna
A1 Sitia, Roberto
AB 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 show that AQP8 gating is mediated by persulfidation of cysteine 53 (C53). Treatment with H2S is sufficient to block H2O2 entry in unstressed cells. Silencing cystathionine beta-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.
PB American Association for the Advancement of Science
SN 2375-2548
YR 2018
FD 2018-05-02
LK https://hdl.handle.net/10016/39178
UL https://hdl.handle.net/10016/39178
LA eng
NO This work was supported in part through grants from the Associazione Italiana Ricerca sul Cancro (IG 2016-18824 to R.S. and IG 2016-15434 to A.R.), the Fondazione Cariplo (2015-0591 to R.S.), the Ministero della Salute (PE-2011-02352286 to R.S. and RF-2013-02354880 to G.M.), the Telethon (GGP15059 to R.S.), and the "Cinque per mille"; (to A.R.). G.P.B. was supported by an Emmy Noether grant 1668/1-1 from the Deutsche Forschungsgemeinschaft.
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RD 1 sept. 2024