Ferroptosis – An Iron- and Disorder-dependent Programmed Cell Death

Document Type


Publication Date



ACSL4Acyl-CoA synthetase long-chain family member 4, Acyl-CoA synthetase long-chain family member 4, PCDprogrammed cell death, programmed cell death, GPX4glutathione peroxidase 4, glutathione peroxidase 4, p53tumor protein 53, tumor protein 53, HSPB1heat shock protein beta-1, heat shock protein beta-1, IDPsintrinsically disordered proteins, intrinsically disordered proteins, IDPRsintrinsically disordered protein regions, intrinsically disordered protein regions, FTMTmitochondrial ferritin, mitochondrial ferritin, PPIprotein-protein interaction, protein-protein interaction, PTMspost-translational modifications, post-translational modifications, Programmed cell death, Ferroptosis, Intrinsically disordered proteins, Intrinsically disordered protein region, Proteins structure-function, Post-translational modification

Digital Object Identifier (DOI)



Programmed cell death (PCD) is an integral component of both developmental and pathological features of an organism. Recently, ferroptosis, a new form of PCD that is dependent on reactive oxygen species and iron, has been described. As with apoptosis, necroptosis, and autophagy, ferroptosis is associated with a large set of proteins assembled in protein-protein interaction (PPI) networks, interactability of which is driven by the presence of intrinsically disordered proteins (IDPs) and IDP regions (IDPRs). Previous investigations have identified the prevalence and functionality of IDPs/IDPRs in non-ferroptosis PCD. The intrinsic disorder in protein structures is used to increase the regulatory powers of these processes. As uncontrolled PCD is associated with the onset of various pathological traits, uncovering the association between intrinsic disorder and ferroptosis-related proteins is crucial. To understand this association, 31 human ferroptosis-related proteins were analyzed via a multi-dimensional array of bioinformatics and computational techniques. In addition, a disorder meta-predictor (PONDR® FIT) was implored to look at the evolutionary conservation of intrinsic disorder in these proteins. This study presents evidence that IDPs and IDPRs are prevalent in ferroptosis. The intrinsic disorder found in ferroptosis has far-reaching functional implications related to ferroptosis-related PPIs and molecular interactions.

Was this content written or created while at USF?


Citation / Publisher Attribution

International Journal of Biological Macromolecules, v. 135, p. 1052-1069