Role of cytochrome c heme lyase in the import of cytochrome c into mitochondria

The import of cytochrome c into Neurospora crassa mitochondria was
examined at distinct stages in vitro. The precursor protein,
apocytochrome c, binds to mitochondria with high affinity and
specificity but is not transported completely across the outer
membrane in the absence of conversion to holocytochrome c. The
bound apocytochrome c is accessible to externally added proteases
but at the same time penetrates far enough through the outer
membrane to interact with cytochrome c heme lyase. Formation of a
complex in which apocytochrome c and cytochrome c heme lyase
participate represents the rate-limiting step of cytochrome c
import. Conversion from the bound state to holocytochrome c, on the
other hand, occurs 10-30-fold faster. Association of apocytochrome
c with cytochrome c heme lyase also takes place after solubilizing
mitochondria with detergent. We conclude that the bound
apocytochrome c, spanning the outer membrane, forms a complex with
cytochrome c heme lyase from which it can react further to be
converted to holocytochrome c and be translocated completely into
the intermembrane space.