Metabolic hallmarks of regulated cell death

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.