Ferroptosis-like death in plant cells

Abstract

Ferroptosis is an iron-dependent, oxidative, non-apoptotic form of cell death initially described in mammalian cells. We recently reported that a ferroptosis-like cell death process can be triggered by heat shock in Arabidopsis thaliana. Thus, ferroptosis may be a form of cell death conserved between animals and plants.

Keywords: Arabidopsis; glutathione; iron; reactive oxygen species.

Figure 1.

Molecular mechanisms of ferroptosis in mammalian and plant cells. (A, B) Our current understanding of the pathways leading to ferroptosis in mammalian cells and ferroptosis-like cell death in plant cells. In both cell types, glutathione prevents lethal lipid oxidation. Death can be prevented by the iron chelator ciclopirox (Cpx) or the lipophillic antioxidant ferrostatin-1 (Fer-1). (A) In human cancer cells, cystine import via the system x_c⁻ amino acid antiporter is necessary for glutathione synthesis. Glutathione is used by glutathione peroxidase 4 (GPX4) to suppress lipid oxidation. Inhibitors (pink) of system x_c⁻ or GPX4 ultimately result in iron-dependent lipid oxidation and ferroptotic cell death. Glu: glutamate, Gly: glycine, Cys₂: cystine, Cys: cysteine. PUFA: polyunsaturated fatty acid. (B) In Arabidopsis thaliana root hair cells, 55°C heat shock depletes glutathione by unknown means, possibly leading to inactivation of one or more GPX4 orthologs (AtGPX4). Unlike in human cancer cells, calcium (Ca²⁺) influx is required for ferroptosis-like cell death. It is unknown whether Ca²⁺ contributes to death by acting upstream or downstream of glutathione depletion in plant cells, or how this influx promotes death. EGTA: ethylene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid.