Compositional Flexibility of the ER-Mitochondria Encounter Structure

Yeast mitochondria receive the majority of their lipids from the endoplasmic reticulum (ER) via the heterotetrameric ERMES lipid transport complex. This complex is thought to establish a lipid transporting tube of fixed composition spanning the space between both organelles. Intriguingly, however, some of the lipid-transporting components of the complex can be replaced by an artificial ER-mitochondria tether without lipid transport activity, indicating that ERMES subunits are not all of equal importance for lipid transport. Here, we propose a model whereby lipid transfer by the ERMES complex can occur with various sub-ensembles of ERMES, and minimally with only one of the four members, namely Mmm1. Our results imply flexibility in the composition of the ERMES complex, which might help it accommodate various interorganelle distances.