A comprehensive and standardized system to report lipid structures analyzed by mass spectrometry is essential for the communication and storage of lipidomics data. Herein, an update on both the LIPID MAPS classification system and shorthand notation of lipid structures is presented for lipid categories Fatty Acyls (FA), Glycerolipids (GL), Glycerophospholipids (GP), Sphingolipids (SP), and Sterols (ST). With its major changes, i.e. annotation of ring double bond equivalents and number of oxygens, the updated shorthand notation facilitates reporting of newly delineated oxygenated lipid species as well. For standardized reporting in lipidomics, the hierarchical architecture of shorthand notation reflects the diverse structural resolution powers provided by mass spectrometric assays. Moreover, shorthand notation is expanded beyond mammalian phyla to lipids from plant and yeast phyla. Finally, annotation of atoms is included for the use of stable isotope-labelled compounds in metabolic labelling experiments or as internal standards.This update on lipid classification, nomenclature and shorthand annotation for lipid mass spectra is considered a standard for lipid data presentation.

Protein carbonylation, one of the most harmful irreversible oxidative protein modifications, is considered as a major hallmark of oxidative stress-related disorders. Protein carbonyl measurements are often performed to assess the extent of oxidative stress in the context of cellular damage, aging and several age-related disorders. A wide variety of analytical techniques are available to detect and quantify protein-bound carbonyls generated by metal-catalyzed oxidation, lipid peroxidation or glycation/glycoxidation. Here we review current analytical approaches for protein carbonyl detection with a special focus on mass spectrometry-based techniques. The utility of several carbonyl-derivatization reagents, enrichment protocols and especially advanced mass spectrometry techniques are compared and discussed in detail. Furthermore, the mechanisms and biology of protein carbonylation are summarized based on recent high-throughput proteomics data.

Ferroptosis, a non-apoptotic form of cell death marked by iron-dependent lipid peroxidation1, has a key role in organ injury, degenerative disease and vulnerability of therapy-resistant cancers2. Although substantial progress has been made in understanding the molecular processes relevant to ferroptosis, additional cell-extrinsic and cell-intrinsic processes that determine cell sensitivity toward ferroptosis remain unknown. Here we show that the fully reduced forms of vitamin K—a group of naphthoquinones that includes menaquinone and phylloquinone3—confer a strong anti-ferroptotic function, in addition to the conventional function linked to blood clotting by acting as a cofactor for γ-glutamyl carboxylase. Ferroptosis suppressor protein 1 (FSP1), a NAD(P)H-ubiquinone reductase and the second mainstay of ferroptosis control after glutathione peroxidase-44,5, was found to efficiently reduce vitamin K to its hydroquinone, a potent radical-trapping antioxidant and inhibitor of (phospho)lipid peroxidation. The FSP1-mediated reduction of vitamin K was also responsible for the antidotal effect of vitamin K against warfarin poisoning. It follows that FSP1 is the enzyme mediating warfarin-resistant vitamin K reduction in the canonical vitamin K cycle6. The FSP1-dependent non-canonical vitamin K cycle can act to protect cells against detrimental lipid peroxidation and ferroptosis.

No abstract