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. Author manuscript; available in PMC: 2020 May 30.
Published in final edited form as: Cell. 2019 Apr 25;177(6):1507–1521.e16. doi: 10.1016/j.cell.2019.03.045

Figure 2-. FXN is unique among the ISC assembly machinery in its ability to be rescued by hypoxia.

Figure 2-

(A) Model of Fe-S cluster biosynthesis in eukaryotic cells. (B) Growth defects of gene CRISPR knock-outs are shown across 342 cancer cell lines from the Cancer Dependency Map, demonstrating that the Fe-S machinery is more essential (lower CERES score) than most genes and that ISCU, NFS1 and LYRM4 are more essential than FXN. Histograms are normalized via the kernel density function to equalize the area under each curve. (C) Three-day proliferation assay of K562 cells KO for the Fe-S assembly machinery- FXN, ISCU, NFS1 or LYRM4- vs. control cells. Cells were grown in 21% O2, 1% O2 or 21% O2 with 75μM FG-4592 (D) Three-day proliferation assay of K562 cells KO for FXN or the Fe-S cluster transfer machinery- GLRX5, HSCB or CIAO3- vs. control cells. Cells were grown in 21% O2, 1% O2 or 21% O2 with 75μM FG-4592 (E) Three-day proliferation assay of control or FXN KO K562 cells in 21% O2, overexpressing different subunits of the Fe-S assembly machinery, including the previously described ISCUM140I bypass mutant. All bar plots show mean ± SD. **=p < 0.01, ***=p < 0.001, ****=p < 0.0001. One-way ANOVA with Bonferroni’s post-test. See also Figure S2.