Ferroptosis Mechanisms and Imaging Techniques

Ferroptosis is a form of regulated cell death driven by iron-dependent lipid peroxidation and characterised by the accumulation of reactive oxygen species (ROS) within membrane phospholipids. Central to its control are the import of iron via transferrin receptor 1, the synthesis of glutathione, and the activity of glutathione peroxidase 4 (GPX4), which detoxifies lipid hydroperoxides. Disruption of redox homeostasis through depletion of cystine or inhibition of GPX4 catalyses a feed-forward cycle of membrane damage. Imaging advancements have sought to visualise these key molecular events in vivo, employing magnetic particle imaging, targeted fluorescent probes and near-infrared sensors to map iron flux, ROS generation and perturbed antioxidant systems. Such tools bridge mechanistic insight with translational applications in ischaemia-reperfusion injury, neurodegeneration and oncology, enabling early detection, quantification and spatiotemporal monitoring of ferroptotic processes.

Research from Nature Portfolio

Recent studies have uncovered a pivotal role for Golgi apparatus integrity in ferroptosis regulation. Chemical disruption of Golgi morphology was shown to trigger iron-dependent lipid peroxidation and cell death, effects that were reversed by canonical ferroptosis inhibitors. Conversely, sublethal modulation of cystine uptake or partial suppression of GPX4 activity conferred protection against Golgi stress, revealing a reciprocal interplay between secretory pathway homeostasis and lipid redox control. These findings place organelle stress at the centre of ferroptotic susceptibility and point to novel targets for intervention in diseases linked to dysregulated redox balance.

Ferroptosis Mechanisms and Imaging Techniques publication trend

The graph below shows the total number of articles in ferroptosis mechanisms and imaging techniques across all publications each year (not limited to Nature Index journals).

Technical terms

Ferroptosis: Iron-dependent form of regulated cell death driven by lipid peroxidation.

Lipid peroxidation: Oxidative degradation of polyunsaturated fatty acids in cell membranes.

Glutathione peroxidase 4 (GPX4): Enzyme that reduces lipid hydroperoxides using glutathione.

Transferrin receptor 1 (TfR1): Cell-surface protein mediating iron uptake and indicating ferroptotic activity.

Magnetic particle imaging (MPI): Non-invasive technique using magnetic nanoparticles for quantitative imaging.

Near-infrared (NIR) fluorescent probe: Optical sensor emitting in the NIR range for deep tissue visualisation.

Reactive oxygen species (ROS): Chemically reactive oxygen derivatives that drive oxidative stress.

References

1. Quantitative visualization of myocardial ischemia-reperfusion-induced cardiac lesions via ferroptosis magnetic particle imaging. Theranostics (2024).
2. Golgi stress mediates redox imbalance and ferroptosis in human cells. Communications Biology (2018).
3. Near-infrared fluorescent probe for hydrogen sulfide: high-fidelity ferroptosis evaluation in vivo during stroke. Chemical Science (2022).
4. Enhanced TfR1 Recognition of Myocardial Injury after Acute Myocardial Infarction with Cardiac Fibrosis via Pre-Degrading Excess Fibrotic Collagen. Biology (2024).