PRDX6 dictates ferroptosis sensitivity by directing cellular selenium utilization.

Selenium-dependent glutathione peroxidase 4 (GPX4) is the guardian of ferroptosis, preventing unrestrained (phospho)lipid peroxidation by reducing phospholipid hydroperoxides (PLOOH). However, the contribution of other phospholipid peroxidases in ferroptosis protection remains unclear. We show that cells lacking GPX4 still exhibit substantial PLOOH-reducing capacity, suggesting a contribution of alternative PLOOH peroxidases.

Synthesis of Unprotected Cyclic Peptide Methylene Dithioacetals by Rhodium-Catalyzed Oxidation of Methanol to Formaldehyde.

In the presence of a rhodium catalyst, unprotected peptide dithiols possessing two cysteine residues are efficiently converted to their corresponding cyclic methylene dithioacetals in a mixed solvent of methanol and water (4:1) under an oxygen atmosphere (1 atm). The slow formation of formaldehyde inhibits side reactions by maintaining its concentration at a low level, which is a key feature of this reaction. This method can be applied to peptide dithiols containing amino acids such as Gly, Ala, Ser, Lys, Met, Phe, Tyr, and His and provides cyclic methylene dithioacetals without being affected by other functional groups.

Antioxidant action of persulfides and polysulfides against free radical-mediated lipid peroxidation.

Hydrogen sulfide, hydropersulfides, and hydropolysulfides have been revealed to play important physiological roles such as cell signaling and protection against oxidative stress, but the underlying mechanisms and dynamics of action remain elusive. It is generally accepted that these species act by two-electron redox mechanisms, while the involvement of one-electron redox chemistry has received less attention. In this study, the radical-scavenging activity of hydrogen persulfide, hydrogen polysulfides (HSH  = 2-4), and diallyl- or dialkyl-sulfides (RSR,  = 1-4) was measured.

Rhodium-Catalyzed Synthesis of Peptide Polysulfides by Insertion of Sulfur into Unprotected Peptide Disulfides.

A rhodium-catalyzed insertion of sulfur into unprotected peptide disulfides in aqueous solvents has been developed, which yields mixtures of trisulfides and tetrasulfides. This method can be applied to peptides containing amino acids such as Gly, Phe, Tyr, Ser, Met, Asp, Gln, and Lys and provides polysulfides with various amino acid residues without being affected by functional groups. A reaction can be conducted on a gram scale.