Large MERCs induced by Gp78 and the OMM–ER linker present distinct shape signatures. (A) The 95th quantile of MERC volume per cell (Q95V; largest 5% of MERCs per cell) and number of MERCs per cell larger than the average 500-voxel size of HT-1080 Q95V MERCs are shown for HT-1080 and COS-7 cells, COS-7, and COS-7 cells overexpressing either Gp78 WT, Gp78 RM, or the OMM–ER linker, HeLa and HeLa cells overexpressing either Gp78 WT, Gp78 RM, or the OMM–ER linker, HT-1080, and Gp78 KO HT-1080 cells, HT-1080 cells transfected with siCTL and siRRBP1, and Gp78 KO HT-1080 cells transfected with siCTL and siRRBP1. (B) Representative cells whose Q95V is closest to the mean Q95V for HT-1080 cells, for COS-7 or HeLa cells overexpressing Gp78 WT, and for COS-7 cells overexpressing the OMM–ER linker were selected for analysis. For the Q95V contacts of each cell, we compute shape features: height, sphericity, and planarity. The comparison shows that the COS-7 OMM–ER linker–induced contacts have a markedly different shape signature compared to those present in HT-1080 and Gp78 overexpressing COS-7 or HeLa cells (i.e., riboMERCS). Averaged over cell, two-sided non-parametric Mann–Whitney test, n = 3 independent biological replicates, ≥30 cells/condition per experiment; *P < 0.05; **P < 0.01; ***P < 0.001.