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Using a genome-wide CRISPR screen, mitochondrial ferredoxin (FDX1), and lipoyl synthase (LIAS) were identified as key regulators of Cu toxicity, 2,257 and genetic knockout of either FDX1 or LIAS leads to an accumulation of pyruvate and -ketoglutarate, reducing protein lipoylation and inhibiting Cu-induced cell death (Fig