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Shiro Bannai reported in 1977 that withdrawal of cystine (see Figure 1 for glossary of key terms in ferroptosis), the oxidized form of cysteine, caused cell death that correlated with glutathione depletion and could be prevented by treatment with vitamin E (Bannai et al., 1977)

This mitochondrial fraction is functionally critical, as demonstrated by the restoration of ferroptosis sensitivity in CHAC1-null cells through expression of a mitochondrially targeted CHAC1 (Ward et al., 2024)

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It also serves as a standard for quantifying intracellular GSH:GSSG ratios in oxidative-stress assays