Journal
SCIENCE ADVANCES
Volume 4, Issue 5, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.aar5770
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Funding
- Associazione Italiana Ricerca sul Cancro [IG 2016-18824, IG 2016-15434]
- Fondazione Cariplo [2015-0591]
- Ministero della Salute [PE-2011-02352286, RF-2013-02354880]
- Telethon [GGP15059]
- Cinque per mille
- Deutsche Forschungsgemeinschaft [1668/1-1]
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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.
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