MOLECULAR MECHANISMS OF CYTOCHROME-C BIOGENESIS - 3 DISTINCT SYSTEMS

The past IO years have heralded remarkable progress in the understandi ng of the biogenesis of c-type cytochromes. The hallmark of c-type cyt ochrome synthesis is the covalent ligation of haem vinyl groups to two cysteinyl residues of the apocytochrome (at a Cys-Xxx-Yyy-Cys-His sig nature motif), From genetic, genomic and biochemical studies, it is cl ear that three distinct systems have evolved in nature to assemble thi s ancient protein. In this review, common principles of assembly for a ll systems and the molecular mechanisms predicted for each system are summarized. Prokaryotes, plant mitochondria and chloroplasts use eithe r system I or II, which are each predicted to use dedicated mechanisms for haem delivery, apocytochrome ushering and thioreduction, Accessor y proteins of systems I and II cc-ordinate the positioning of these tw o substrates at the membrane surface for covalent ligation, The third system has evolved specifically in mitochondria of fungi, invertebrate s and vertebrates. For system III, a pivotal role is played by an enzy me called cytochrome c haem lyase (CCHL) in the mitochondrial intermem brane space.