The breadth of ubiquitinated non-protein substrates, their abundance, and cellular roles are currently unclear, since current ubiquitinomic and proteomic techniques are blind to non-proteinaceous modifications.
Enzymatic inhibitors are indispensable tools for dissecting biological pathways and developing therapeutic interventions1. They are broadly categorized by their binding sites and mechanisms of action. Among these, orthosteric inhibitors, which bind to the catalytic site and directly compete with substrates, have been extensively explored due to their predictable structure-activity relationships. However, such inhibitors are typically substrate-agnostic, as their mechanism relies solely on blocking the active site.
Ferroptosis, a major mechanism of non-apoptotic programmed cell death, critically regulates the homeostasis and functionality of peripheral CD4+ and CD8+ T cells. Here we demonstrate that in mouse, resistance of T cells to ferroptosis depends critically on the composition of standard rodent diets, and that dietary effects on ferroptosis have a crucial role in regulation of T cell homeostasis and immune responses.