Cytochrome c biogenesis System I: An intricate process catalyzed by a maturase supercomplex?

Abstract

Cytochromes c are ubiquitous heme proteins that are found in most living organisms and are essential for various energy production pathways as well as other cellular processes. Their biosynthesis relies on a complex post-translational process, called cytochrome c biogenesis, responsible for the formation of stereo-specific thioether bonds between the vinyl groups of heme b (protoporphyrin IX-Fe) and the thiol groups of apocytochromes c heme-binding site (C1XXC2H) cysteine residues. In some organisms this process involves up to nine (CcmABCDEFGHI) membrane proteins working together to achieve heme ligation, designated the Cytochrome c maturation (Ccm)-System I. Here, we review recent findings related to the Ccm-System I found in bacteria, archaea and plant mitochondria, with an emphasis on protein interactions between the Ccm components and their substrates (apocytochrome c and heme). We discuss the possibility that the Ccm proteins may form a multi subunit supercomplex (dubbed “Ccm machine”), and based on the currently available data, we present an updated version of a mechanistic model for Ccm.

During Cytochrome c Maturation CcmI Chaperones the Class I Apocytochromes until the Formation of Their b-Type Cytochrome Intermediates

“…In addition, holoCcmE is known to form a complex with CcmF in Escherichia coli (38). Altogether, these findings indicate that the heme ligation complex, CcmFHI, contains CcmE and CcmG, possibly forming a large "maturase supercomplex" (15).…”

“…The class II soluble high-spin cytochrome cЈ is involved in NO detoxification (13), and the class III membrane-attached pentaheme c-type cytochrome DorC con-veys electrons from the Q/QH 2 pool to dimethyl sulfoxide (DMSO) 3 reducing it to dimethylsulfide (14). R. capsulatus and other ␣-and ␥-proteobacteria, archaea, and mitochondria of plants and red algae carry out the process of covalent heme ligation to the c-type apocytochromes via a membrane complex, designated as cytochrome c maturation (Ccm) System I (15)(16)(17)(18). The overall process relies on several cellular pathways, including post-translational modification and secretion of c-type apocytochromes and the folding and degradation of proteins, as well as maintenance of a suitable thioredox environment conducive to cofactor insertion.…”

“…The overall process relies on several cellular pathways, including post-translational modification and secretion of c-type apocytochromes and the folding and degradation of proteins, as well as maintenance of a suitable thioredox environment conducive to cofactor insertion. The Ccm complex involves nine membrane proteins (CcmABCDEFGHI) that are responsible for the chaperoning of c-type apocytochromes and heme as well as their covalent ligation (15).…”

Mitochondrial cytochrome c biogenesis: no longer an enigma

“…We emphasize studies on the human HCCS, but it is likely that these mechanisms are common to all HCCS proteins, which are widely distributed in eukaryotes (see Box 1). Interestingly, the prokaryotic cyt c biogenesis pathways, called Systems I and II (previously reviewed in [15, 20, 23-25]) are retained in some eukaryotes (Box 1); these pathways are addressed (Box 2) with respect to mechanistic insight gained from our new understanding of HCCS.…”

Bacterial Electron Transfer Chains Primed by Proteomics

“…Haems that act in electron transfer, such as c-and b-type haems, or in catalysis by terminal oxidases and nitric oxide reductases (b-, a-and o-type haems) are localised at the outer aspect of the membranes. So, before incorporation into a subunit(s), these molecules have to be translocated as well, which is realised by the cytochrome c maturation machinery (Kranz, Richard-Fogal, Taylor, & Frawley, 2009;Verissimo & Daldal, 2014). Periplasmic subunits can be attached to the membrane by covalently bound lipid molecules.…”