ER–mitochondria
junctionsarethoughttobethemajor
gateway
for lipid exchange between mitochondria and the
rest
of the cell. 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 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 [33]. ERMES is found
in
yeast but not in higher eukaryotes [34]. 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 [35
] and mitochondria from these
cells
have altered phospholipid composition including
significantly
reduced levels of PE and CL [33,36–39It
may be that the ERMES complex is involved in moving
lipids
in specific conditions, such as during mitochondriadivision
or mitophagy, in which the ERMES complex has
been
found to be involved [9,40]. Alternatively, ERMEmay
not directly facilitate lipid exchange. In either case, is
clear that other complexes that tether the ER and
mitochondria
and facilitate lipid exchange remain to be
identified.