Biogenesis of cytochrome c1

The biogenesis of cytochrome c1 involves a number of steps
including: synthesis as a precursor with a bipartite signal
sequence, transfer across the outer and inner mitochondrial
membranes, removal of the first part of the presequence in the
matrix, reexport to the outer surface of the inner membrane,
covalent addition of heme, and removal of the remainder of the
presequence. In this report we have focused on the steps of heme
addition, catalyzed by cytochrome c1 heme lyase, and of proteolytic
processing during cytochrome c1 import into mitochondria. Following
translocation from the matrix side to the intermembrane-space side
of the inner membrane, apocytochrome c1 forms a complex with
cytochrome c1 heme lyase, and then holocytochrome c1 formation
occurs. Holocytochrome c1 formation can also be observed in
detergent-solubilized preparations of mitochondria, but only after
apocytochrome c1 has first interacted with cytochrome c1 heme lyase
to produce this complex. Heme linkage takes place on the
intermembrane- space side of the inner mitochondrial membrane and
is dependent on NADH plus a cytosolic cofactor that can be replaced
by flavin nucleotides. NADH and FMN appear to be necessary for
reduction of heme prior to its linkage to apocytochrome c1. The
second proteolytic processing of cytochrome c1 does not take place
unless the covalent linkage of heme to apocytochrome c1 precedes
it. On the other hand, the cytochrome c1 heme lyase reaction itself
does not require that processing of the cytochrome c1 precursor to
intermediate size cytochrome c1 takes place first. In conclusion,
cytochrome c1 heme lyase catalyzes an essential step in the import
pathway of cytochrome c1, but it is not involved in the
transmembrane movement of the precursor polypeptide. This is in
contrast to the case for cytochrome c in which heme addition is
coupled to its transport directly across the outer membrane into
the intermembrane space.