A morphological view on mitochondrial protein targeting

Mitochondrial protein targeting includes both intramitochondrial
sorting of proteins encoded by the organellar genome and import and
subsequent sorting of nuclear encoded precursor proteins. Only a
few proteins are encoded by the mitochondrial genome and
synthesized in the organellar matrix. These include predominantly
inner membrane proteins that are perhaps co-translationally
inserted into this membrane. Biochemical data suggest that
insertion into the inner membrane may be confined to the inner
boundary membrane. Ultrastructurally, however, a preferential
association of ribosomes with either inner boundary or cristae
membranes has not been established. The majority of the
mitochondrial proteins are nuclear encoded and synthesized as
precursors in the cytosol. Electron microscopic studies revealed
that import of precursor proteins is generally confined to sites
where both mitochondrial envelope membranes are closely apposed. In
line with these observations, biochemical studies indicated that
precursor proteins destined for the inner membrane or matrix have
to interact with the energized inner membrane to allow complete
passage of the precursor through the outer membrane. As a
consequence, the mitochondrial envelope membranes have to be in
close proximity at protein import sites. In isolated mitochondria
distinct sites (designated as contact sites) exist where both
envelope membranes are closely apposed and presumably stably
associated. In situ, however, mitochondrial boundary membranes are
in close proximity over large areas that cover almost the entire
mitochondrial periphery. Consequently, the relative area of the
mitochondrial surface, where both boundary membranes are in
sufficient proximity for allowing protein translocation, is
generally larger in situ compared to that in isolated organelles.
Immunocytochemical localization studies showed a rather random
distribution of components of the mitochondrial protein
translocation machinery over the entire mitochondrial surface and
not confined to contact sites. Based on these ultrastructral data
and recent biochemical findings we propose that mitochondrial
protein import sites are dynamic in nature and include relatively
labile regions of close association of the boundary membranes. In
vitro, however, mitochondrial protein import may preferentially
take place at or near the presumably stable contact sites.