We are still just beginning to understand how these close-contacts are established.
A number of ER–mitochondria tethering complexes have been identified in mammalian cells but it is not currently known if
they are required for lipid exchange between these organelles.
An important breakthrough in our understanding of ER–mitochondrial tethering and lipid trafficking was
the discovery of the ER–mitochondria encounter structure (ERMES), a complex that localizes to junctions
between the ER and mitochondria.
ERMES is found in yeast but not in higher eukaryotes.
Interestingly,three of the proteins in ERMES contain lipid-binding SMP domains and thus could facilitate lipid exchange
between the ER and mitochondria.
Consistent with this possibility, cells lacking ERMES have reduced ER–mitochondria contacts and mitochondria from these
cells have altered phospholipid composition including significantly reduced levels of PE and CL.
It may be that the ERMES complex is involved in moving lipids in specific conditions, such as during mitochondrial
division or mitophagy, in which the ERMES complex has been found to be involved .
Alternatively, ERMES may not directly facilitate lipid exchange. In either case, it is clear that other complexes that tether the ER and mitochondria and facilitate lipid exchange remain to be identified.