Iron-sulfur cluster deficiency can be sensed by IRP2 and regulates iron homeostasis and sensitivity to ferroptosis independent of IRP1 and FBXL5
Erdem M. Terzi, Vladislav O. Sviderskiy, Samantha Alvarez, Gabrielle C. Whiten, Richard Possemato
Abstract
concentrations, ISC deficiency enhances IRP2 binding to target mRNAs independent of IRP1, FBXL5, and changes in IRP2 protein level. Deletion of both IRP1 and IRP2 abolishes the iron-starvation response, preventing its activation by ISC synthesis inhibition. These findings will inform strategies to manipulate ferroptosis sensitivity and help illuminate the mechanism underlying ISC biosynthesis disorders, such as Friedreich's ataxia.
Topics & Concepts
Iron homeostasisIron deficiencyCluster (spacecraft)HomeostasisIron–sulfur clusterSensitivity (control systems)BiologyChemistryCell biologyMedicineBiochemistryComputer scienceInternal medicineMetabolismAnemiaEngineeringElectronic engineeringEnzymeProgramming languageIron Metabolism and DisordersRNA modifications and cancerFerroptosis and cancer prognosis