Figure 1. Models of phospholipid transfer by ERMES between the ER and mitochondrial OM. (Upper) Lipid carrier model. Mmm1 may change the relative geometry to Mdm12 from the tail (Mmm1)-to-head (Mdm12) contact to the head (Mmm1)-to-head (Mdm12) contact, so that the phospholipid molecule bound to the hydrophobic pocket of Mmm1 can be transferred to the one of Mdm12 through the outlets of the both pockets at the head-to-head interface between Mmm1 and Mdm12. Upon receiving the phospholipid molecule from Mmm1, Mdm12 may switch the partner from Mmm1 to Mdm34, with changing the relative geometry to Mdm34 from the tail (Mdm12)-to-head (Mdm34) to the head (Mdm12)-to-head (Mdm34) contact for further lipid transfer. (Lower) Continuous conduit model. The phospholipid molecule extracted by Mmm1 from the ER membrane may diffuse through the hydrophobic conduit from Mmm1 to reach Mdm34 via Mdm12, and then is inserted into the mitochondrial OM by Mdm34.