Lipid-derived electrophiles inhibit the function of membrane channels during ferroptosis.

The therapeutic targeting of ferroptosis requires full understanding of the molecular mechanism of this regulated cell death pathway. While lipid-derived electrophiles (LDEs), including 4-hydroxy-2-nonenal (4-HNE), are important biomarkers of ferroptosis, a functional role for these highly reactive species in ferroptotic cell death execution has not been established. Here, through mechanistic characterization of LDE-detoxification impairment, we demonstrate that LDEs mediate altered protein function during ferroptosis.

Live-cell imaging reveals impaired detoxification of lipid-derived electrophiles is a hallmark of ferroptosis.

The central mechanism in ferroptosis linking lipid hydroperoxide accumulation with cell death remains poorly understood. Although lipid hydroperoxides are known to break down to reactive lipid-derived electrophiles (LDEs), the ability of cells to detoxify increasing LDE levels during ferroptosis has not been studied. Here, we developed an assay (ElectrophileQ) correlating the cellular retention excretion of a fluorogenic lipophilic electrophile (AcroB) that enables live-cell assessment of the glutathione-mediated LDE conjugation and adduct export steps of the LDE detoxification pathway.

Beyond DPPH: Use of Fluorescence-Enabled Inhibited Autoxidation to Predict Oxidative Cell Death Rescue.

"Antioxidant activity" is an often invoked, but generally poorly characterized, molecular property. Several assays are available to determine antioxidant activity, the most popular of which is based upon the ability of a putative antioxidant to reduce 2,2-diphenyl-1-picrylhydrazyl. Here, we show that the results of this assay do not correlate with the potency of putative antioxidants as inhibitors of ferroptosis, the oxidative cell death modality associated with (phospho)lipid peroxidation.

A dormant BODIPY-acrolein singlet oxygen photosensitizer intracellularly activated upon adduct formation with cysteine residues.

Here we report the activatable photosensitizer BromoAcroB, a brominated BODIPY dye incorporating a reactive acrolein warhead. The acrolein moiety serves as an intramolecular switch, deactivating the BODIPY dye in its singlet and triplet excited states via internal conversion. Thiolate addition to this moiety disables the intramolecular quenching mechanism restoring the photosensitizing properties of the parent dye, characterized by a quantum yield of singlet oxygen photosensitization of 0.

A novel small RNA is important for biofilm formation and pathogenicity in Pseudomonas aeruginosa.

The regulation of biofilm development requires multiple mechanisms and pathways, but it is not fully understood how these are integrated. Small RNA post-transcriptional regulators are a strong candidate as a regulatory mechanism of biofilm formation. More than 200 small RNAs in the P.

A Continuous Visible Light Spectrophotometric Approach To Accurately Determine the Reactivity of Radical-Trapping Antioxidants.

Inhibited autoxidations-monitored either by O2 consumption or hydroperoxide formation-are the most reliable way to obtain kinetic and stoichiometric information on the activity of radical-trapping antioxidants (RTAs). While many comparatively simple "antioxidant assays" (e.g.