BBA - Bioenergetics (v.1817, #6)
Editorial Board (i).
Biogenesis/assembly of respiratory enzyme complexes by Jonathan Hosler (849-850).
Understanding mitochondrial complex I assembly in health and disease by Masakazu Mimaki; Xiaonan Wang; Matthew McKenzie; David R. Thorburn; Michael T. Ryan (851-862).
Complex I (NADH:ubiquinone oxidoreductase) is the largest multimeric enzyme complex of the mitochondrial respiratory chain, which is responsible for electron transport and the generation of a proton gradient across the mitochondrial inner membrane to drive ATP production. Eukaryotic complex I consists of 14 conserved subunits, which are homologous to the bacterial subunits, and more than 26 accessory subunits. In mammals, complex I consists of 45 subunits, which must be assembled correctly to form the properly functioning mature complex. Complex I dysfunction is the most common oxidative phosphorylation (OXPHOS) disorder in humans and defects in the complex I assembly process are often observed. This assembly process has been difficult to characterize because of its large size, the lack of a high resolution structure for complex I, and its dual control by nuclear and mitochondrial DNA. However, in recent years, some of the atomic structure of the complex has been resolved and new insights into complex I assembly have been generated. Furthermore, a number of proteins have been identified as assembly factors for complex I biogenesis and many patients carrying mutations in genes associated with complex I deficiency and mitochondrial diseases have been discovered. Here, we review the current knowledge of the eukaryotic complex I assembly process and new insights from the identification of novel assembly factors. This article is part of a Special Issue entitled: Biogenesis/Assembly of Respiratory Enzyme Complexes.► A large number of subunits are assembled to form a mature mitochondrial complex I. ► Assembly factors required for complex I biogenesis have been newly identified. ► Defects of assembly factors and complex I subunits have been discovered in human. ► Analyses of complex I biogenesis provide an updated model for its assembly process.
Keywords: Mitochondria; Respiratory chain; Complex I; Complex I deficiency; Assembly factor;
Disruption of individual nuo-genes leads to the formation of partially assembled NADH:ubiquinone oxidoreductase (complex I) in Escherichia coli by Heiko Erhardt; Stefan Steimle; Vera Muders; Thomas Pohl; Julia Walter; Thorsten Friedrich (863-871).
The proton-pumping NADH:ubiquinone oxidoreductase, respiratory complex I, couples the electron transfer from NADH to ubiquinone with the translocation of protons across the membrane. In Escherichia coli the complex is made up of 13 different subunits encoded by the so-called nuo-genes. Mutants, in which each of the nuo-genes was individually disrupted by the insertion of a resistance cartridge were unable to assemble a functional complex I. Each disruption resulted in the loss of complex I-mediated activity and the failure to extract a structurally intact complex. Thus, all nuo-genes are required either for the assembly or the stability of a functional E. coli complex I. The three subunits comprising the soluble NADH dehydrogenase fragment of the complex were detected in the cytoplasm of several nuo-mutants as one distinct band after BN-PAGE. It is discussed that the fully assembled NADH dehydrogenase fragment represents an assembly intermediate of the E. coli complex I. A partially assembled complex I bound to the membrane was detected in the nuoK and nuoL mutants, respectively. Overproduction of the ΔNuoL variant resulted in the accumulation of two populations of a partially assembled complex in the cytoplasmic membranes. Both populations are devoid of NuoL. One population is enzymatically active, while the other is not. The inactive population is missing cluster N2 and is tightly associated with the inducible lysine decarboxylase. This article is part of a Special Issue entitled: Biogenesis/Assembly of Respiratory Enzyme Complexes.► Respiratory complex I from E. coli consists of 13 subunits. ► All corresponding genes are essential for the assembly of the complex. ► A soluble fragment of the complex is accumulated in various complex I mutants. ► A membranous fragment accumulates in the ΔnuoL and ΔnuoK mutants. ► Overproduction leads to a variant associated with inducible lysine decarboxylase.
Keywords: NADH dehydrogenase; Complex I; Assembly; Escherichia coli; Chaperone; Lysine decarboxylase;
Reprint of: Biogenesis of the cytochrome bc 1 complex and role of assembly factors by Pamela M. Smith; Jennifer L. Fox; Dennis R. Winge (872-882).
The cytochrome bc 1 complex is an essential component of the electron transport chain in most prokaryotes and in eukaryotic mitochondria. The catalytic subunits of the complex that are responsible for its redox functions are largely conserved across kingdoms. In eukarya, the bc 1 complex contains supernumerary subunits in addition to the catalytic core, and the biogenesis of the functional bc 1 complex occurs as a modular assembly pathway. Individual steps of this biogenesis have been recently investigated and are discussed in this review with an emphasis on the assembly of the bc 1 complex in the model eukaryote Saccharomyces cerevisiae. Additionally, a number of assembly factors have been recently identified. Their roles in bc 1 complex biogenesis are described, with special emphasis on the maturation and topogenesis of the yeast Rieske iron–sulfur protein and its role in completing the assembly of functional bc 1 complex. This article is part of a Special Issue entitled: Biogenesis/Assembly of Respiratory Enzyme Complexes.► Biogenesis of bc 1 complexes occurs as a modular assembly pathway. ► Stable assembly intermediates accumulate in mutants stalled in biogenesis. ► Recently identified assembly factors function in the formation of assembly intermediates.
Keywords: Cytochrome bc 1 complex; Rieske Fe/S protein; Bcs1; Mzm1; Cyt1;
Biogenesis and assembly of eukaryotic cytochrome c oxidase catalytic core by Ileana C. Soto; Flavia Fontanesi; Jingjing Liu; Antoni Barrientos (883-897).
Eukaryotic cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial respiratory chain. COX is a multimeric enzyme formed by subunits of dual genetic origin which assembly is intricate and highly regulated. The COX catalytic core is formed by three mitochondrial DNA encoded subunits, Cox1, Cox2 and Cox3, conserved in the bacterial enzyme. Their biogenesis requires the action of messenger-specific and subunit-specific factors which facilitate the synthesis, membrane insertion, maturation or assembly of the core subunits. The study of yeast strains and human cell lines from patients carrying mutations in structural subunits and COX assembly factors has been invaluable to identify these ancillary factors. Here we review the current state of knowledge of the biogenesis and assembly of the eukaryotic COX catalytic core and discuss the degree of conservation of the players and mechanisms operating from yeast to human. This article is part of a Special Issue entitled: Biogenesis/Assembly of Respiratory Enzyme Complexes.► Cytochrome c oxidase (COX) is the terminal mitochondrial respiratory chain enzyme. ► The catalytic core of COX is formed by three mitochondrial DNA encoded subunits. ► A large number of nuclear encoded ancillary factors are necessary for COX biogenesis. ► Core subunit synthesis and maturation are key regulatory points during COX assembly.
Keywords: Mitochondria; Cytochrome c oxidase; COX catalytic core; COX assembly;
Biogenesis of cbb 3-type cytochrome c oxidase in Rhodobacter capsulatus by Seda Ekici; Grzegorz Pawlik; Eva Lohmeyer; Hans-Georg Koch; Fevzi Daldal (898-910).
The cbb 3-type cytochrome c oxidases (cbb 3-Cox) constitute the second most abundant cytochrome c oxidase (Cox) group after the mitochondrial-like aa 3-type Cox. They are present in bacteria only, and are considered to represent a primordial innovation in the domain of Eubacteria due to their phylogenetic distribution and their similarity to nitric oxide (NO) reductases. They are crucial for the onset of many anaerobic biological processes, such as anoxygenic photosynthesis or nitrogen fixation. In addition, they are prevalent in many pathogenic bacteria, and important for colonizing low oxygen tissues. Studies related to cbb 3-Cox provide a fascinating paradigm for the biogenesis of sophisticated oligomeric membrane proteins. Complex subunit maturation and assembly machineries, producing the c-type cytochromes and the binuclear heme b 3 -CuB center, have to be coordinated precisely both temporally and spatially to yield a functional cbb 3-Cox enzyme. In this review we summarize our current knowledge on the structure, regulation and assembly of cbb 3-Cox, and provide a highly tentative model for cbb 3-Cox assembly and formation of its heme b 3-CuB binuclear center. This article is part of a Special Issue entitled: Biogenesis/Assembly of Respiratory Enzyme Complexes.► Structure-function, regulation and biogenesis of cbb 3-type Cox are reviewed. ► A multistep assembly pathway of the subunits of this membrane enzyme is discussed. ► A model for formation of the heme b 3-CuB center of this enzyme is proposed.
Keywords: cbb 3-type cytochrome c oxidase; Co- or post-translational cofactor insertion; Assembly of membrane proteins; Copper acquisition; Photosynthesis and respiration; Energy transduction;
Thiol redox requirements and substrate specificities of recombinant cytochrome c assembly systems II and III by Cynthia L. Richard-Fogal; Brian San Francisco; Elaine R. Frawley; Robert G. Kranz (911-919).
The reconstitution of biosynthetic pathways from heterologous hosts can help define the minimal genetic requirements for pathway function and facilitate detailed mechanistic studies. Each of the three pathways for the assembly of cytochrome c in nature (called systems I, II, and III) has been shown to function recombinantly in Escherichia coli, covalently attaching heme to the cysteine residues of a CXXCH motif of a c-type cytochrome. However, recombinant systems I (CcmABCDEFGH) and II (CcsBA) function in the E. coli periplasm, while recombinant system III (CCHL) attaches heme to its cognate receptor in the cytoplasm of E. coli, which makes direct comparisons between the three systems difficult. Here we show that the human CCHL (with a secretion signal) attaches heme to the human cytochrome c (with a signal sequence) in the E. coli periplasm, which is bioenergetically (p-side) analogous to the mitochondrial intermembrane space. The human CCHL is specific for the human cytochrome c, whereas recombinant system II can attach heme to multiple non-cognate c-type cytochromes (possessing the CXXCH motif.) We also show that the recombinant periplasmic systems II and III use components of the natural E. coli periplasmic DsbC/DsbD thiol-reduction pathway. This article is part of a Special Issue entitled: Biogenesis/Assembly of Respiratory Enzyme Complexes.► Human CCHL matures human cytochrome c in the E. coli periplasm but at significantly lower levels than cytoplasmic CCHL ► E. coli DsbC and DsbD mediate thiol reduction for recombinant systems II and III ► The major feature of apocytochromes recognized by CcsBA is CXXCH ► Residues in addition to CXXCH are important for apocytochrome recognition by CCHL
Keywords: Cytochrome c assembly; CCHL; Heme attachment; Periplasmic; Thioreduction;
Heme A biosynthesis by Lars Hederstedt (920-927).
Respiration in plants, most animals and many aerobic microbes is dependent on heme A. This is a highly specialized type of heme found as prosthetic group in cytochrome a-containing respiratory oxidases. Heme A differs structurally from heme B (protoheme IX) by the presence of a hydroxyethylfarnesyl group instead of a vinyl side group at the C2 position and a formyl group instead of a methyl side group at position C8 of the porphyrin macrocycle. Heme A synthase catalyzes the formation of the formyl side group and is a poorly understood heme-containing membrane bound atypical monooxygenase. This review presents our current understanding of heme A synthesis at the molecular level in mitochondria and aerobic bacteria. This article is part of a Special Issue entitled: Biogenesis/Assembly of Respiratory Enzyme Complexes.Display Omitted► Heme A is a specialised type of heme found in respiratory cytochrome oxidases. ► Heme A and chlorophyll b biosynthesis have common features. ► Heme A synthase is a membrane bound heme-containing atypical monooxygenase ► Heme A synthase has evolved from a variant with 4 transmembrane segments.
Keywords: Cytochrome biogenesis; Heme synthesis; CtaA; COX15; Oxidase assembly;
Role of Surf1 in heme recruitment for bacterial COX biogenesis by Achim Hannappel; Freya A. Bundschuh; Bernd Ludwig (928-937).
Biogenesis of the mitochondrial cytochrome c oxidase (COX) is a highly complex process involving subunits encoded both in the nuclear and the organellar genome; in addition, a large number of assembly factors participate in this process. The soil bacterium Paracoccus denitrificans is an interesting alternative model for the study of COX biogenesis events because the number of chaperones involved is restricted to an essential set acting in the metal centre formation of oxidase, and the high degree of sequence homology suggests the same basic mechanisms during early COX assembly. Over the last years, studies on the P. denitrificans Surf1 protein shed some light on this important assembly factor as a heme a binding protein associated with Leigh syndrome in humans. Here, we summarise our current knowledge about Surf1 and its role in heme a incorporation events during bacterial COX biogenesis. This article is part of a Special Issue entitled: Biogenesis/Assembly of Respiratory Enzyme Complexes. ► Paracoccus denitrificans is a suitable model for COX biogenesis. ► Surf1 abstracts heme a from its site of synthesis, heme a synthase. ► Surf1 provides a protein-bound heme a pool for COX biogenesis. ► Surf1 facilitates heme a incorporation into COX subunit I.
Keywords: Respiratory chain; Heme/copper oxidases; Oxidase biogenesis; Heme a; Binuclear centre; Heme incorporation;
The fictile coordination chemistry of cuprous-thiolate sites in copper chaperones by M. Jake Pushie; Limei Zhang; Ingrid J. Pickering; Graham N. George (938-947).
Copper plays vital roles in the active sites of cytochrome oxidase and in several other enzymes essential for human health. Copper is also highly toxic when dysregulated; because of this an elaborate array of accessory proteins have evolved which act as intracellular carriers or chaperones for the copper ions. In most cases chaperones transport cuprous copper. This review discusses some of the chemistry of these copper sites, with a view to some of the structural factors in copper coordination which are important in the biological function of these chaperones. The coordination chemistry and accessible geometries of the cuprous oxidation state are remarkably plastic and we discuss how this may relate to biological function. This article is part of a Special Issue entitled: Biogenesis/Assembly of Respiratory Enzyme Complexes.Display Omitted► The coordination chemistry of cuprous copper shows remarkable plasticity. ► Cuprous ions can deform and reorganize with remarkably low energies. ► The plasticity of the cuprous oxidation state may enable transport.
Keywords: Copper transport; Cuprous thiolate clusters; Copper homeostasis; EXAFS;
Differential affinity of BsSCO for Cu(II) and Cu(I) suggests a redox role in copper transfer to the CuA center of cytochrome c oxidase by Bruce C. Hill; Diann Andrews (948-954).
SCO (synthesis of cytochrome c oxidase) proteins are involved in the assembly of the respiratory chain enzyme cytochrome c oxidase acting to assist in the assembly of the CuA center contained within subunit II of the oxidase complex. The CuA center receives electrons from the reductive substrate ferrocytochrome c, and passes them on to the cytochrome a center. Cytochrome a feeds electrons to the oxygen reaction site composed of cytochrome a 3 and CuB. CuA consists of two copper ions positioned within bonding distance and ligated by two histidine side chains, one methionine, a backbone carbonyl and two bridging cysteine residues. The complex structure and redox capacity of CuA present a potential assembly challenge. SCO proteins are members of the thioredoxin family which led to the early suggestion of a disulfide exchange function for SCO in CuA assembly, whereas the copper binding capacity of the Bacillus subtilis version of SCO (i.e., BsSCO) suggests a direct role for SCO proteins in copper transfer. We have characterized redox and copper exchange properties of apo- and metalated-BsSCO. The release of copper (II) from its complex with BsSCO is best achieved by reducing it to Cu(I). We propose a mechanism involving both disulfide and copper exchange between BsSCO and the apo-CuA site. This article is part of a Special Issue entitled: Biogenesis/Assembly of Respiratory Enzyme Complexes.Display Omitted► BsSCO binds Cu(II) with much higher affinity than Cu(I). ► Binding of Cu(II) follows a two-step process leading to stable complex. ► At high ionic strength Cu(II)/BsSCO binding is transient. ► BsSCO–Cu(II) complex is reducible and resulting BsSCO–Cu(I) complex undergoes facile metal exchange.
Keywords: SCO proteins; BsSCO; CuA assembly; Cytochrome c oxidase; Copper binding; Metal transfer;
The roles of Rhodobacter sphaeroides copper chaperones PCuAC and Sco (PrrC) in the assembly of the copper centers of the aa 3-type and the cbb 3-type cytochrome c oxidases by Audie K. Thompson; Jimmy Gray; Aimin Liu; Jonathan P. Hosler (955-964).
The α proteobacter Rhodobacter sphaeroides accumulates two cytochrome c oxidases (CcO) in its cytoplasmic membrane during aerobic growth: a mitochondrial-like aa 3-type CcO containing a di-copper CuA center and mono-copper CuB, plus a cbb 3-type CcO that contains CuB but lacks CuA. Three copper chaperones are located in the periplasm of R. sphaeroides, PCuAC, PrrC (Sco) and Cox11. Cox11 is required to assemble CuB of the aa 3-type but not the cbb 3-type CcO. PrrC is homologous to mitochondrial Sco1; Sco proteins are implicated in CuA assembly in mitochondria and bacteria, and with CuB assembly of the cbb 3-type CcO. PCuAC is present in many bacteria, but not mitochondria. PCuAC of Thermus thermophilus metallates a CuA center in vitro, but its in vivo function has not been explored. Here, the extent of copper center assembly in the aa 3- and cbb 3-type CcOs of R. sphaeroides has been examined in strains lacking PCuAC, PrrC, or both. The absence of either chaperone strongly lowers the accumulation of both CcOs in the cells grown in low concentrations of Cu2 +. The absence of PrrC has a greater effect than the absence of PCuAC and PCuAC appears to function upstream of PrrC. Analysis of purified aa 3-type CcO shows that PrrC has a greater effect on the assembly of its CuA than does PCuAC, and both chaperones have a lesser but significant effect on the assembly of its CuB even though Cox11 is present. Scenarios for the cellular roles of PCuAC and PrrC are considered. The results are most consistent with a role for PrrC in the capture and delivery of copper to CuA of the aa 3-type CcO and to CuB of the cbb 3-type CcO, while the predominant role of PCuAC may be to capture and deliver copper to PrrC and Cox11. This article is part of a Special Issue entitled: Biogenesis/Assembly of Respiratory Enzyme Complexes.► The presence of Sco strongly enhances the assembly of CuA of aa 3-type CcO. ► The presence of Sco strongly enhances the assembly of CuB of cbb 3-type CcO. ► The Cu chaperone PCuAC enhances assembly but requires the presence of Sco.
Keywords: cbb 3-type cytochrome c oxidase; aa 3-type cytochrome c oxidase; Copper chaperone; Copper center assembly; CuA; Sco protein;
Biogenesis of inner membrane proteins in Escherichia coli by Joen Luirink; Zhong Yu; Samuel Wagner; Jan-Willem de Gier (965-976).
The inner membrane proteome of the model organism Escherichia coli is composed of inner membrane proteins, lipoproteins and peripherally attached soluble proteins. Our knowledge of the biogenesis of inner membrane proteins is rapidly increasing. This is in particular true for the early steps of biogenesis — protein targeting to and insertion into the membrane. However, our knowledge of inner membrane protein folding and quality control is still fragmentary. Furthering our knowledge in these areas will bring us closer to understand the biogenesis of individual inner membrane proteins in the context of the biogenesis of the inner membrane proteome of Escherichia coli as a whole. This article is part of a Special Issue entitled: Biogenesis/Assembly of Respiratory Enzyme Complexes.► Our knowledge of the biogenesis of individual IMPs is rapidly increasing. ► Our understanding of the biogenesis of the IM proteome as a system is only scant. ► Using global approaches will further our understanding of the IM proteome as a system.
Keywords: E. coli; Inner membrane; Membrane protein; Biogenesis;