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Mitochondrial dysfunction leads to the decrease of NAD + level, resulting in lysosomal acidification and impaired autophagy, and induces ferroptosis, involving the accumulation of iron in lysosomes and lipid peroxidation

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When intracellular iron is low, iron-sulfur (Fe-S) is released from the active site of the IRP, permitting IRP to bind to the IRE of divalentmetal-iontransporter-1 (DMT1) and transferrin receptor (TfR) gene transcripts to activate TfR translation, while IRPs bind to ferroportin (FPN) gene transcripts to inhibit FPN translation, resulting in the promotion of free iron absorption to increase the intracellular concentration and reduce the excretion of cellular iron (Reichert et al., 2020