The subcellular landscape of ferroptosis: A cellular organelle perspective

Junren Dai

1,2

Xingfeng Du

Ying Hu

1,2,3,*

*Correspondence to: Ying Hu, School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, Heilongjiang, China. E-mail: huying@hit.edu.cn

Ferroptosis Oxid Stress. 2027;3:202632. 10.70401/fos.2026.0043

Received: July 05, 2026Accepted: September 16, 2026Published: September 16, 2026

This manuscript is made available in its unedited form to allow early access to the reported findings. Further editing will be completed before final publication. As such, the content may include errors, and standard legal disclaimers are applicable.

Abstract

Ferroptosis is a regulated form of cell death driven by iron-dependent lipid peroxidation. Its execution depends not only on the amount of lipid peroxides, but also on where oxidizable lipids, redox-active iron, reactive oxygen species, and antioxidant defenses are distributed within cells. This review summarizes current evidence for organelle-resolved regulation of ferroptosis and oxidative stress, with emphasis on the endoplasmic reticulum, peroxisomes, mitochondria, lysosomes, lipid droplets, and phase-separated condensates. We discuss how lipid remodeling, ether lipid synthesis, mitochondrial metabolism and local antioxidant defense, ferritinophagy, lysosomal lipid peroxidation, and lipid droplet-mediated fatty acid buffering influence ferroptosis sensitivity. We also summarize how organelle-specific redox defenses and stress-adaptive signaling pathways may shape therapeutic responses. Together, these studies show that ferroptosis is regulated by coordinated changes in lipid metabolism, iron handling, and antioxidant capacity across distinct subcellular compartments.

Keywords

Ferroptosis, lipid peroxidation, organelles, spatiotemporal specificity

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Dai J, Du X, Hu Y. The subcellular landscape of ferroptosis: A cellular organelle perspective. Ferroptosis Oxid Stress. 2027;3:202632. https://doi.org/10.70401/fos.2026.0043