Genetic interactions of SCS3 and YFT2 map to sphingolipid, phospholipid, and inositol phosphate synthesis pathways.

Cross-talk between the different pathways is illustrated by the central role of PI synthesis and DAG production/utilization. The arrangement of the steps in the Kennedy and CDP-DAG pathways for the synthesis of PC is modified from Carman and Han [47]. The role of the ERMES complex in transporting PS from the ER to the mitochondria for conversion to PE and its return to the ER [50] is represented by a red box. Genes encoding all four components of the complex (MDM10, MDM12, MDM34 and MMM1) exhibited alleviating interactions when both SCS3 and YFT2 were deleted (Table S1; the alleviating interaction between MDM10 and the SCS3 YFT2 double deletion was identified with relaxed criteria, 38 pixel size difference, p = 0.006, ε = 0.18). The synthesis of PE and PC from lysoPE and lyso PC is omitted for clarity. The steps in the synthesis of inositol phosphates are modified from York [52]. The pathway for the synthesis of complex sphingolipids is modified from Dickson [53]. Steps involving genes that interact genetically with SCS3 and/or YFT2 show the gene name above three boxes which indicate the relative strength and sign of the interactions. Aggravating (green) and alleviating (red) interactions are ordered from left to right for the scs3Δ, yft2Δ and scs3Δ yft2Δ strains using the values in Table S1. A colorbar shows the intensity of the interactions. Phosphatidic acid, PA; diacylglycerol, DAG; triglyceride, TG; lipid droplet, LD, Gro, glycerol; DHAP, dihydroxyacetone phosphate; Glu, glucose; Ins, inositol; PME, phosphatidyl monomethylethanolamine; PDE, phosphatidyl dimethylethanolamine; Etn, ethanolamine; Cho, choline., dihydrosphingosine, DHS; phytosphingosine, PHS; inositolphosphoceramide, IPC; mannosyl-inositolphosphoceramide, MIPC; mannosyl-diinositolphosphoceramide, M(IP)2.