Sorting pathways of mitochondrial inner membrane proteins

Two distinct pathways of sorting and assembly of nuclear-encoded
mitochondrial inner membrane proteins are described. In the first
pathway, precursor proteins that carry amino-terminal targeting
signals are initially translocated via contact sites between both
mitochondrial membranes into the mitochondrial matrix. They become
proteolytically processed, interact with the 60-kDa heat-shock
protein hsp60 in the matrix and are retranslocated to the inner
membrane. The sorting of subunit 9 of Neurospora crassa Fo-ATPase
has been studied as an example. Fo subunit 9 belongs to that class
of nuclear-encoded mitochondrial proteins which are evolutionarily
derived from a prokaryotic ancestor according to the endosymbiont
hypothesis. We suggest that after import into mitochondria, these
proteins follow the ancestral sorting and assembly pathways
established in prokäryotes (conservative sorting). On the other
hand, ADP/ATP carrier was found not to require interaction with
hsp60 for import and assembly. This agrees with previous findings
that the ADP/ATP carrier possesses non-amino-terminal targeting
signals and uses a different import receptor to other mitochondrial
precursor proteins. It is proposed that the ADP/ATP carrier
represents a class of mitochondrial inner membrane proteins which
do not have a prokaryotic equivalent and thus appear to follow a
non-conservative sorting pathway.