Biogenesis of mitochondrial c-type cytochromes

Cytochromesc andc 1 are essential components of the mitochondrial
respiratory chain. In both cytochromes the heme group is covalently
linked to the polypeptide chain via thioether bridges. The location
of the two cytochromes is in the intermembrane space; cytochromec
is loosely attached to the surface of the inner mitochondrial
membrane, whereas cytochromec 1 is firmly anchored to the inner
membrane. Both cytochromec andc 1 are encoded by nuclear genes,
translated on cytoplasmic ribosomes, and are transported into the
mitochondria where they become covalently modified and assembled.
Despite the many similarities, the import pathways of cytochromec
andc 1 are drastically different. Cytochromec 1 is made as a
precursor with a complex bipartite presequence. In a first step the
precursor is directed across outer and inner membranes to the
matrix compartment of the mitochondria where cleavage of the first
part of the presequence takes place. In a following step the
intermediate-size form is redirected across the inner membrane;
heme addition then occurs on the surface of the inner membrane
followed by the second processing reaction. The import pathway of
cytochromec is exceptional in practically all aspects, in
comparison with the general import pathway into mitochondria.
Cytochromec is synthesized as apocytochromec without any additional
sequence. It is translocated selectively across the outer membrane.
Addition of the heme group, catalyzed by cytochromec heme lyase, is
a requirement for transport. In summary, cytochromec 1 import
appears to follow a conservative pathway reflecting features of
cytochromec 1 sorting in prokaryotic cells. In contrast,
cytochromec has invented a rather unique pathway which is
essentially non-conservative.