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13C-tracing and the analysis of cystathionine synthase and cystathioninase levels revealed the metabolic landscape attributable to cysteine deprivation, and the disconnection between the methionine cycle and the transsulfuration pathway

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Notably, L2HG-induced ferroptosis occurs independently of impaired cystine uptake, transsulfuration pathway activity, or increased GPX4-mediated GSH utilization, revealing a non-canonical ferroptosis mechanism driven by enhanced GSH catabolism

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