Structurally, it is the only GPX isoform with a monomeric conformation and a unique catalytic tetrad including Sec, Gln81, Trp136, and Asn137 that enables it to reduce complex hydroperoxides in situ even within membranes ( Transcriptionally, GPX4 expression is promoted by Nrf2 and ATF4 in response to oxidative or endoplasmic reticulum stress
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59 , 60 , 61 , 62 The reversible oxidative modifications of cysteine residues imply an important mechanism whereby ROS and RNS can readily interact with these molecules, dictating protein function and cell signaling that can be regulated by GSH
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