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A novel amine moiety‐based fluorescent probe (BA) was prepared using diphenylacetylene as fluorophore and amino group as acceptor. The probe achieves detection of formaldehyde through fluorescence enhancement by inhibition the photoinduced electron transfer (PET) between diphenylacetylene and amino group. And the different formaldehyde detection performance of 2‐(phenylethynyl)aniline (BA‐1), 3‐(phenylethynyl)aniline (BA‐2) and 4‐(phenylethynyl)aniline (BA‐3) indicates that the position of amino recognition group on the benzene ring of diphenylacetylene has a significant impact on the detection ability of this type fluorescent probe. When the amino group is in the ortho‐position of the benzene ring, probe BA‐1 can rapidly enhance the fluorescence intensity within 20 min with limit of detection as low as 0.75 μM; When the amino group is located in meta‐position of benzene ring, the solution of BA‐2 also exhibited a certain degree of fluorescence enhancement, but it is weaker than BA‐1; When the amino group is at the para‐position of benzene ring, BA‐3 has almost no response to formaldehyde. [ABSTRACT FROM AUTHOR]

The Cystine-xCT transporter-Glutathione (GSH)-GPX4 axis is the canonical pathway to protect against ferroptosis. While not required for ferroptosis-inducing compounds (FINs) targeting GPX4, FINs targeting the xCT transporter require mitochondria and its lipid peroxidation to trigger ferroptosis. However, the mechanism underlying the difference between these FINs is still unknown. Given that cysteine is also required for coenzyme A (CoA) biosynthesis, here we show that CoA supplementation specifically prevents ferroptosis induced by xCT inhibitors but not GPX4 inhibitors. We find that, auranofin, a thioredoxin reductase inhibitor, abolishes the protective effect of CoA. We also find that CoA availability determines the enzymatic activity of thioredoxin reductase, but not thioredoxin. Importantly, the mitochondrial thioredoxin system, but not the cytosolic thioredoxin system, determines CoA-mediated ferroptosis inhibition. Our data show that the CoA regulates the in vitro enzymatic activity of mitochondrial thioredoxin reductase (TXNRD2) by covalently modifying the thiol group of cysteine (CoAlation) on Cys-483. Replacing Cys-483 with alanine on TXNRD2 abolishes its in vitro enzymatic activity and ability to protect cells from ferroptosis. Targeting xCT to limit cysteine import and, therefore, CoA biosynthesis reduced CoAlation on TXNRD2, an effect that was rescued by CoA supplementation. Furthermore, the fibroblasts from patients with disrupted CoA metabolism demonstrate increased mitochondrial lipid peroxidation. In organotypic brain slice cultures, inhibition of CoA biosynthesis leads to an oxidized thioredoxin system, mitochondrial lipid peroxidation, and loss in cell viability, which were all rescued by ferrostatin-1. These findings identify CoA-mediated post-translation modification to regulate the thioredoxin system as an alternative ferroptosis protection pathway with potential clinical relevance for patients with disrupted CoA metabolism., Competing Interests: Conflict of interest statement The authors have declared that no conflict of interest exists.