Regulation of ferroptosis by inter-organellar metabolic signaling network
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Ferroptosis and Oxidative Stress
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Regulation of ferroptosis by inter-organellar metabolic signaling network

Luna Zhang
#
,
Zefang Bimo Zhao
#
,
Weitao Li
#,*
,
Jiajun Zhu
*
*Correspondence to: Weitao Li, State Key Laboratory of Molecular Oncology, School of Basic Medical Sciences, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China. E-mail: weitaol@mail.tsinghua.edu.cn
Jiajun Zhu, State Key Laboratory of Molecular Oncology, School of Basic Medical Sciences, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China. E-mail: zhujiajun@tsinghua.edu.cn
Ferroptosis Oxid Stress. 2026;2:202628. 10.70401/fos.2026.0038
Received: June 12, 2026Accepted: July 28, 2026Published: July 28, 2026
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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 form of regulated cell death driven by iron-dependent lipid peroxidation, and is therefore intrinsically coupled to cellular redox metabolism. Progression of ferroptosis is regulated by an integrated network of metabolic signaling pathways that involve inter-organellar communication. In this Review, we synthesize recent progress in the field that have advanced our understanding of the metabolic determinants of ferroptosis. We discuss key metabolites which participate in the execution and prevention of ferroptosis, describe major signaling axes that impinge on regulating these metabolic activities to determine cellular ferroptosis sensitivity, and highlight how compartmentalized metabolism within and across distinct intracellular organelles collectively shape ferroptosis progression. Together, this Review aims to provide a framework that unifies metabolic state, signaling plasticity and organellar cooperation as a mechanistic basis of ferroptosis, underscoring its implications in the pathogenesis of various diseases including cancer.

Keywords

Cellular metabolism, metabolic signaling, subcellular compartments

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Zhang L, Zhao ZB, Li W, Zhu J. Regulation of ferroptosis by inter-organellar metabolic signaling network. Ferroptosis Oxid Stress. 2026;2:202628. https://doi.org/10.70401/fos.2026.0038

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