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. 2024 Jan 31;626(8000):874–880. doi: 10.1038/s41586-023-06985-7

Fig. 1. The E3 ligase SIFI protects cells during mitochondrial import stress.

Fig. 1

a, Outline of the synthetic lethality screen. sgRNA, singe guide RNA. b, ΔUBR4 cells are sensitive to the inhibition of mitochondrial import or ETC function. Darker grey dots represent the top 5% CasTLE score genes. c, Screen validation by depleting hits in mixtures of GFP-labelled WT and mCherry-labelled ΔUBR4 cells, reported as (ΔUBR4sgRNA/WTsgRNA)/(ΔUBR4sgCNTRL/WTsgCNTRL). sgCNTRL, control sgRNA. d, Chemical mitochondrial stress or growth in galactose-depleted conditions selectively depletes ΔUBR4 cells, reported as (ΔUBR4treatment/WTtreatment)/(ΔUBR4control/WTcontrol). e, Endogenous Flag–UBR4 and KCMF1–Flag were affinity purified, and binding partners were determined by mass spectrometry. TSCnorm, normalized total spectral counts. f, Cells lacking KCMF1 or the endogenous KCMF1-binding, calmodulin-binding (CALM) or UBR domains of UBR4 were depleted of TIMM8A and assessed by competition, reported as (UBR4(Δdomain)sgTIMM8A/WTsgTIMM8A)/(UBR4(Δdomain)sgCNTRL/WTsgCNTRL). UBR4 domain map visualizing location of endogenous domain deletions.