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Peer-reviewedCC BY 4.0Cell Research

Metabolic hallmarks of regulated cell death

  • Rui Kang1
  • Xin Chen2,3
  • Guido Kroemer4,5,6,7
  • Daolin Tang1
7 affiliations
  1. 1Department of Surgery, UT Southwestern Medical Center, Dallas, Texas USA
  2. 2Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Disease, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China
  3. 3Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China
  4. 4Centre de Recherche des Cordeliers, Université Paris Cité, Sorbonne Université, Inserm, Paris, France
  5. 5Institut Gustave Roussy, Université Paris-Saclay, INSERM US23/CNRS UAR 3655, Metabolomics and Cell Biology Platforms, UMS AMMICa, Villejuif Cedex, France
  6. 6Institut du Cancer Paris CARPEM, Department of Biology, Hôpital Européen Georges-Pompidou, AP-HP, Paris, France
  7. 7Centre de Recherche des Cordeliers, Équipe labellisée par la Ligue contre le cancer, Paris, France
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Abstract

Regulated cell death (RCD) is characterized by distinct molecular execution mechanisms, but its initiation, progression, and biological consequences are increasingly recognized as being shaped by cellular metabolism. Bioenergetic state, redox homeostasis, nutrient availability, metal ion metabolism, inflammatory metabolism, and organelle function collectively determine cellular susceptibility to death and influence the activation and execution of diverse RCD programs. In this review, we synthesize the metabolic hallmarks of established, independently validated, and recently proposed forms of RCD, highlighting both their mechanistic diversity and their extensive metabolic convergence. We then examine the endogenous mechanisms that maintain metabolic homeostasis and discuss how their disruption reshapes cell death responses in human disease and therapeutic contexts. Together, these insights provide a guide to the metabolic landscape of RCD and reveal metabolism not only as a modifier of cell death, but as a fundamental determinant of when, how, and with what consequences cells die. We conclude by discussing key conceptual and mechanistic challenges and emerging opportunities for therapeutically exploiting the metabolic control of RCD.

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Cite

BibTeXRIS
BibTeX
@article{kang2026metabolic,
  title = {{Metabolic hallmarks of regulated cell death}},
  author = {Rui Kang and Xin Chen and Guido Kroemer and Daolin Tang},
  journal = {Cell Research},
  year = {2026},
  month = oct,
  doi = {10.1038/s41422-026-01306-9},
  url = {https://doi.org/10.1038/s41422-026-01306-9},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Metabolic hallmarks of regulated cell death
AU  - Rui Kang
AU  - Xin Chen
AU  - Guido Kroemer
AU  - Daolin Tang
PY  - 2026
DA  - 2026/10/20
JO  - Cell Research
DO  - 10.1038/s41422-026-01306-9
UR  - https://doi.org/10.1038/s41422-026-01306-9
AB  - Regulated cell death (RCD) is characterized by distinct molecular execution mechanisms, but its initiation, progression, and biological consequences are increasingly recognized as being shaped by cellular metabolism. Bioenergetic state, redox homeostasis, nutrient availability, metal ion metabolism, inflammatory metabolism, and organelle function collectively determine cellular susceptibility to death and influence the activation and execution of diverse RCD programs. In this review, we synthesize the metabolic hallmarks of established, independently validated, and recently proposed forms of RCD, highlighting both their mechanistic diversity and their extensive metabolic convergence. We then examine the endogenous mechanisms that maintain metabolic homeostasis and discuss how their disruption reshapes cell death responses in human disease and therapeutic contexts. Together, these insights provide a guide to the metabolic landscape of RCD and reveal metabolism not only as a modifier of cell death, but as a fundamental determinant of when, how, and with what consequences cells die. We conclude by discussing key conceptual and mechanistic challenges and emerging opportunities for therapeutically exploiting the metabolic control of RCD.
SN  - 1001-0602
SN  - 1748-7838
ER  -