This review proposes a conceptual framework in which cellular metabolism acts as a 'gatekeeper' of regulated cell death (RCD), examining how bioenergetic capacity, redox balance, lipid composition, and metal availability shape cell fate across death modalities including apoptosis and ferroptosis.
The authors position RCD pathways along a metabolic continuum — from energy-dependent apoptosis to chemistry-driven ferroptosis — arguing that organelle-resolved metabolism and inter-organelle communication spatially coordinate death decisions, and that metabolic reprogramming can redirect cell fate.
This is a review/framework paper with no original experimental data; the proposed metabolic continuum model is conceptual and awaits prospective validation in disease contexts.
Targeting metabolic dependencies (e.g., redox balance, lipid metabolism, metal availability) may offer new strategies to promote or suppress specific cell death pathways in diseases such as cancer, neurodegeneration, and ischemia. Clinicians should watch for translational studies testing metabolic interventions that exploit these RCD vulnerabilities.
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