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Necroptosis can also be materialized as a result of activation of the signaling pathways, due to DNA damage, which leads to the release of apoptosis-related factors from the mitochondrial intermembrane space, followed by the activation of the DNA damagerelated enzyme poly(ADP-ribose) polymerase (PARP) [213]

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The resulting catastrophic energy deficit is a primary physiological driver of post-exertional malaise (PEM) or 'crashes,' where even minor, everyday activities trigger a disproportionate and prolonged exacerbation of profound fatigue, muscle weakness, and cognitive impairment

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