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At least 757 records · Page 42Linked to original sources
PubMed2006

p37 is a p97 adaptor required for Golgi and ER biogenesis in interphase and at the end of mitosis.

We previously reported that p97/p47-assisted membrane fusion is important for the reassembly of organelles at the end of mitosis, but not for their maintenance during interphase. We have now identified a p97 adaptor protein, p37, which forms a complex with p97 in the cytosol and localizes to the Golgi and ER. siRNA experiments revealed that p37 is required for Golgi and ER biogenesis. Injection of anti-p37 antibodies into cells at different cell cycle stages showed that p37 plays an important role in both Golgi and ER maintenance during interphase as well as in their reassembly at the end of mitosis. In an in vitro Golgi reassembly assay, the p97/p37 complex has membrane fusion activity. In contrast to the p97/p47 pathway, this pathway requires p115-GM130 tethering and SNARE GS15, but not syntaxin5. Interestingly, although VCIP135 is also required, its deubiquitinating activity is unnecessary for p97/p37-mediated activities.

Adaptor Proteins, Signal Transducing↗
PubMed2006

GABP complex regulates transcription of eIF6 (p27BBP), an essential trans-acting factor in ribosome biogenesis.

Eukaryotic initiation factor 6 (eIF6, alias p27BBP) is required for the biogenesis of 60S ribosomal subunits. eIF6 expression levels are tightly regulated in vivo, where they correlate with cellular growth. We analyzed how transcriptional regulation of eIF6 is achieved. We show that the human eIF6 promoter contains consensus sites for the GABP (GA-binding protein) transcription factor complex. Functional analysis of GABP consensus sequences by point mutations, EMSA (electrophoretic mobility shift assay) and a dominant negative mutant indicates that GABP is essential for eIF6 promoter activity. These data strengthen the hypothesis that GABP is a global regulator of ribosome synthesis.

Carrier Proteins↗
PubMed2006

Prokaryotic and eukaryotic monothiol glutaredoxins are able to perform the functions of Grx5 in the biogenesis of Fe/S clusters in yeast mitochondria.

The Saccharomyces cerevisiae monothiol glutaredoxin Grx5 participates in the mitochondrial biogenesis of iron-sulfur clusters. Grx5 homologues exist in organisms from bacteria to humans. Chicken (cGRX5) and human (hGRX5) homologues contain a mitochondrial targeting sequence, suggesting a mitochondrial localization for these two proteins. We have compartmentalized the Escherichia coli and Synechocystis sp. homologues, and also cGRX5 and hGRX5, in the mitochondrial matrix of a yeast grx5 mutant. All four heterologous proteins rescue the defects of the mutant. The chicken cGRX5 gene was significantly expressed throughout the embryo stages in different tissues. These results underline the functional conservation of Grx5 homologues throughout evolution.

Animals↗
PubMed2006

A variant System I for cytochrome c biogenesis in archaea and some bacteria has a novel CcmE and no CcmH.

C-type cytochromes are characterized by post-translational covalent attachment of heme to thiols that occur in a Cys-Xxx-Xxx-Cys-His motif. Three distinct biogenesis systems are known for this heme attachment. Archaea are now shown to contain a significantly modified form of cytochrome c maturation System I (the Ccm system). The most notable adaptation relative to the well-studied apparatus from proteobacteria and plants is a novel form of the heme chaperone CcmE, lacking the highly conserved histidine that covalently binds heme and is essential for function in Escherichia coli. In most archaeal CcmEs this histidine, normally found in a His-Xxx-Xxx-Xxx-Tyr motif, is replaced by a cysteine residue that occurs in a Cys-Xxx-Xxx-Xxx-Tyr motif. The CcmEs from two halobacteria contain yet another form of CcmE, having HxxxHxxxH approximately corresponding in alignment to the H/CxxxY motif. The CxxxY-type of CcmE is, surprisingly, also found in some bacterial genomes (including Desulfovibrio species). All of the modified CcmEs cluster together in a phylogenetic tree, as do other Ccm proteins from the same organisms. Significantly, CcmH is absent from all of the complete archaeal genomes we have studied, and also from most of the bacterial genomes that have CxxxY-type CcmE.

Amino Acid Sequence↗
PubMed2006

Light-responsive transcriptional regulation of the suf promoters involved in cyanobacterium Synechocystis sp. PCC 6803 Fe-S cluster biogenesis.

The widely conserved SUF system is involved in Fe-S cluster repair and biogenesis. In cyanobacterium Synechocystis sp. PCC 6803, transcription of the sufBCDS operon encoding the Suf complex is negatively regulated by the upstream sufR gene encoded by the complementary strand. In this report, two promoters for the sufBCDS operon (P1 and P2) and another promoter for sufR (PsufR) was identified, and it was shown that P1 was activated by a shift to high light conditions. We also showed that Thermosynechococcus SufR negatively regulated P1 and PsufR but not P2, in a reconstituted in vitro transcription system using His(6)-tagged RNA polymerase.

Base Sequence↗
PubMed2005

Biogenesis of cytochrome oxidase-sophisticated assembly lines in the mitochondrial inner membrane.

Biogenesis of the cytochrome oxidase complex in the mitochondrial inner membrane depends on the concerted action of a variety of proteins. Recent studies shed light on this biological assembly process revealing an astonishingly complex procedure by which the different subunits of the enzymes are put together and the required cofactors are supplied. In this review we present a hypothetical model for the assembly process of cytochrome oxidase based on the current knowledge of the functions of specific assembly factors. According to this model the two largest subunits of the complex are first equipped with their respective cofactors on independent assembly lines. Prior to their assembly with the residual subunits that complete the whole complex, these two subcomplexes remain bound to substrate-specific chaperones. We propose that these chaperones, Mss51 for subunit 1 and Cox20 for subunit 2, control the coordinate assembly process to prevent potentially harmful redox reactions of unassembled or misassembled subunits.

Amino Acid Sequence↗
PubMed2006

The pleiotropic Arabidopsis frd mutation with altered coordination of chloroplast biogenesis, cell size and differentiation, organ size and number.

In higher plants, plastid development must be tightly coordinated with cell and organ development. In this paper, a novel T-DNA-mutagenized Arabidopsis line showing chlorotic leaves and minute stature was identified in a genetic screen for altered chloroplast development. The mutation corresponded to a single locus on chromosome IV and was associated with insertion of the T-DNA. This locus was named FARFADET and resulted in pleiotropic effects on chloroplast biogenesis, cell size and differentiation, organ size and number. Thus, in contrast with previously described chlorotic mutants, frd mutants were affected not only in chloroplast development and chlorophyll accumulation, but also in cell and organ development. Alteration of differentiation affected different cell types such as leaf epidermal cells, trichomes, mesophyll cells, and columella cells. A major effect on mesophyll cell differentiation was the lack of palisadic parenchyma and absence of grana stacks. Moreover, meristem size and lateral meristem initiation were affected. Genetic and molecular characterisation showed that the T-DNA insertion generated 41 bp deletion in a potential miRNA precursor. The predicted miRNA target genes were involved in plant development and stress. It is therefore hypothesized that the frd mutation had affected coordination of cell developmental span and the control of the division-differentiation balance.

Arabidopsis↗
PubMed2006

Membrane biogenesis of subunit II of cytochrome bo oxidase: contrasting requirements for insertion of N-terminal and C-terminal domains.

The membrane assembly of the respiratory complexes requires the membrane insertases Oxa1 in mitochondria and YidC in bacteria. Oxa1 is responsible for the insertion of the mitochondrial cytochrome c oxidase subunit II (CoxII). Here, we investigated whether YidC, the bacterial Oxa1 homolog, plays a crucial role in the assembly of the bacterial subunit II (CyoA) of cytochrome bo oxidase. CyoA spans the membrane twice and is made with a cleavable signal peptide. We find that translocation of the short N-terminal domain of CyoA is YidC-dependent. In contrast, both the SecA/SecYEG complex and YidC are required for translocation of the large C-terminal domain. By studying the N-terminal domain of CyoA alone, we find that translocation is unaffected when SecE is depleted, suggesting that the YidC insertase on its own catalyzes membrane insertion of the N-terminal region of CyoA. Strikingly, we find that the translocation of the N-terminal domain is a prerequisite for translocation of the C-terminal domain in the full-length CyoA protein because translocation of the large C-terminal domain alone in a truncated CyoA derivative was observed in the absence of YidC. This work shows that the distinct domains of CyoA have different translocation requirements (YidC only and Sec/YidC) and confirms that the membrane biogenesis of subunit II of cytochrome oxidase in bacteria and mitochondria have conserved features.

Adenosine Triphosphatases↗
PubMed2004

On the biogenesis of lipid bodies in ancient eukaryotes: synthesis of triacylglycerols by a Toxoplasma DGAT1-related enzyme.

In mammalian cells, the main stored neutral lipids are triacylglycerol and cholesteryl esters, which are produced by two related enzymes, acyl-CoA:diacylglycerol acyltransferase (DGAT) and acyl-CoA:cholesterol acyltransferase (ACAT), respectively. Very little is known about the metabolism, intracellular storage and function of neutral lipids in many pathogenic lower eukaryotes. In this paper, we have characterized the activity of an important triacylglycerol synthetic enzyme in the protozoan Toxoplasma gondii. A full-length cDNA and gene encoding a T. gondii DGAT1-related enzyme were identified and designated TgDGAT1. The gene is composed of 15 exons and 14 introns, and encodes a protein with a predicted M(r) 63.5kDa, containing signature motifs characteristic of the DGAT1 family. The native protein migrates at 44kDa under reducing conditions. TgDGAT1 is an integral membrane protein localized to the parasite cortical and perinuclear endoplasmic reticulum, with the C-terminus oriented to the lumen of the organelle. When a Saccharomyces cerevisiae mutant strain lacking neutral lipid production is transformed with TgDGAT1 cDNA, a significant DGAT activity is reconstituted, resulting in triacylglycerol synthesis and biogenesis of cytosolic lipid inclusions, resembling lipid bodies in T. gondii. No production of steryl esters is observed upon TgDGAT1 expression in yeast. In contrast to human DGAT1 lacking fatty acid specificity, TgDGAT1 preferentially incorporates palmitate. Our results indicate that parasitic protozoa are also neutral lipid accumulators and illustrate the first example of the existence of a functional DGAT gene in an ancient eukaryote, demonstrating that diacylglycerol esterification is evolutionarily conserved.

Acyltransferases↗
PubMed2004

Perinuclear biogenesis of mutant torsin-A inclusions in cultured cells infected with tetracycline-regulated herpes simplex virus type 1 amplicon vectors.

TorsinA is a novel protein identified in the search for mutations underlying the human neurologic movement disorder, early onset torsion dystonia. Relatively little is understood about the normal function of torsinA or the physiological effects of the codon deletion associated with most cases of disease. Overexpression of wild-type torsinA in cultured cells by DNA transfection results in a reticular distribution of immunoreactive protein that co-localizes with endoplasmic reticulum resident chaperones, while the dystonia-related mutant form accumulates within concentric membrane whorls and nuclear-associated membrane stacks. In this study we examined the biogenesis of mutant torsinA-positive membrane inclusions using tetracycline-regulated herpes simplex virus amplicon vectors. At low expression levels, mutant torsinA was localized predominantly around the nucleus, while at high levels it was also concentrated within cytosolic spheroid inclusions. In contrast, the distribution of wild-type torsinA did not vary, appearing diffuse and reticular at all expression levels. These observations are consistent with descriptions of inducible membrane synthesis in other systems in which cytosolic membrane whorls are derived from multilayered membrane stacks that first form around the nuclear envelope. These results also suggest that formation of mutant torsinA-positive inclusions occurs at high expression levels in culture, whereas the perinuclear accumulation of the mutant protein is present even at low expression levels that are more likely to resemble those of the endogenous protein. These nuclear-associated membrane structures enriched in mutant torsinA may therefore be of greater relevance to understanding how the dystonia-related mutation compromises cellular physiology.

Animals↗
PubMed2005

Oxygen-induced mitochondrial biogenesis in the rat hippocampus.

The hypothesis that damage to mitochondrial DNA by reactive oxygen species increases the activity of nuclear and mitochondrial transcription factors for mitochondrial DNA replication was tested in the in vivo rat brain. Mitochondrial reactive oxygen species generation was stimulated using pre-convulsive doses of hyperbaric oxygen and hippocampal mitochondrial DNA content and neuronal and mitochondrial morphology and cell proliferation were evaluated at 1, 5 and 10 days. Gene expression was subsequently evaluated to assess nuclear and mitochondrial-encoded respiratory genes, mitochondrial transcription factor A, and nuclear respiratory transcription factors-1 and -2. After 1 day, a mitochondrial DNA deletion emerged involving Complex I and IV subunit-encoding regions that was independent of overt neurological or cytological O(2) toxicity, and resolved before the onset of cell proliferation. This damage was attenuated by blockade of neuronal nitric oxide synthase. Compensatory responses were found in nuclear gene expression for manganese superoxide dismutase, mitochondrial transcription factor A, and nuclear respiratory transcription factor-2. Enhanced nuclear respiratory transcription factor-2 binding activity in hippocampus was accompanied by a nearly three-fold boost in mitochondrial DNA content over 5 days. The finding that O(2) activates regional mitochondrial DNA transcription, replication, and mitochondrial biogenesis in the hippocampus may have important implications for maintaining neuronal viability after brain injury.

Animals↗
PubMed2006

Strigol: biogenesis and physiological activity.

The role played by molecules of the strigolactone family in stimulating the germination of seeds of parasitic weeds of the genera Striga, Orobanche and Alectra has never been clearly elucidated. The biogenesis of these unusual terpenoid lactones, originally identified in minute quantities in the root exudates of a small number of host plants and two or three "false hosts", also remains obscure. These lactones, as the chemical signals which initiate the life cycle of Striga, are consequently at the forefront of the Striga research effort. This paper reviews recent key discoveries relating to the biosynthesis and mode of action of strigolactones, and summarises the evidence suggesting that these molecules may be far more widely distributed and have a greater physiological significance than has hitherto been appreciated.

Germination↗
PubMed2005

Biogenesis, molecular regulation and function of plant isoprenoids.

Isoprenoids represent the oldest class of known low molecular-mass natural products synthesized by plants. Their biogenesis in plastids, mitochondria and the endoplasmic reticulum-cytosol proceed invariably from the C5 building blocks, isopentenyl diphosphate and/or dimethylallyl diphosphate according to complex and reiterated mechanisms. Compounds derived from the pathway exhibit a diverse spectrum of biological functions. This review centers on advances obtained in the field based on combined use of biochemical, molecular biology and genetic approaches. The function and evolutionary implications of this metabolism are discussed in relation with seminal informations gathered from distantly but related organisms.

Cytosol↗
PubMed2004

Can endogenous gaseous messengers control mitochondrial biogenesis in mammalian cells?

Mitochondria have been identified as the site of oxidative energy metabolism and of numerous biosynthetic and degradative reactions, which depend on a distinctive mitochondrial structure, with different enzymes and reactions localised in discrete membranes and aqueous compartments. Synthesis and import of mitochondrial components are required for mitochondrial proliferation, but rather than producing new organelles, these processes may facilitate the growth of preexisting mitochondria. Recent evidence indicates that these events are regulated in a complex way by several agonists and environmental conditions, through activation of specific transcription factors and signaling pathways. Some of these are now being elucidated. Generation of nitric oxide (NO) appears to be a novel player in this scenario, possibly acting as a unifying molecular switch to trigger the whole process of the mitochondrial biogenesis.

Animals↗
PubMed2026

Selenoprotein S associates with complexes governing membrane protein biogenesis and translation-associated processes.

Human selenoprotein S (selenos) is part of the integrated cellular stress response and linked to protein quality control and signaling pathways. Consequently, genetic polymorphisms of selenos are associated with increased risks for diabetes, dyslipidemia, and cardiovascular diseases. Determining the specific roles of selenos in these cellular pathways and diseases has been challenging, as selenos associates with a wide range of protein complexes. Thus, to map the cellular functions of selenos and uncover their interconnections, we used affinity purification and in vivo crosslinking to stabilize transient protein interactions, followed by proteomics to record the resulting selenos interactome. Through mapping of selenos protein partners, we found evidence that selenos associates with complexes responsible for the insertion of membrane proteins into the endoplasmic reticulum (ER) bilayer and their connected quality control components. Furthermore, selenos is also part of metabolic, trafficking, and mitochondrial pathways. Notably, proteins involved in translation preferentially associate with selenos when its C-terminal intrinsically disordered segment containing the redox-active motif is accessible. Together, these results identify the C-terminal redox loop of selenos as a central interaction hub connecting translation with ER membrane protein biogenesis and quality control.

Selenoproteins↗
PubMed2006

Non-essential KDO biosynthesis and new essential cell envelope biogenesis genes in the Escherichia coli yrbG-yhbG locus.

In Escherichia coli and most Gram-negative bacteria, KDO (3-deoxy-D-manno-octulosonate), a component of the lipopolysaccharide inner core, is essential for outer membrane biogenesis and cell viability. Two recently identified genes involved in KDO biosynthesis, kdsD and kdsC, belong to the yrbG-yhbG locus where four additional ORFs (yrbG, yrbK, yhbN and yhbG) with unknown function are located. We have constructed six conditional expression mutants in which the arabinose-inducible araBp promoter is respectively located upstream of each gene of the locus. Complementation analysis of these mutants indicates that the locus is organized in at least three operons and that the three distal genes (yrbK, yhbN and yhbG) are essential for E. coli viability. Surprisingly, kdsD and kdsC (encoding a D-arabinose 5-phosphate isomerase and a KDO 8-phosphate phosphatase, respectively) were shown to be non-essential, indicating genetic redundancy for these two functions. A preliminary characterization of the arabinose-dependent mutants under permissive conditions and upon depletion revealed increased sensitivity to hydrophobic toxic chemicals, suggesting that the mutants have a defective outer membrane. These genes may thus be implicated in cell envelope integrity.

Aldose-Ketose Isomerases↗
PubMed2005

Iron-sulfur-protein biogenesis in eukaryotes.

Iron-sulfur (Fe-S) clusters (ISCs) are versatile, ancient co-factors of proteins that are involved in electron transport, enzyme catalysis and regulation of gene expression. The synthesis of ISCs and their insertion into apoproteins involves the function of complex cellular machineries. In eukaryotes, the mitochondrial ISC-assembly machinery is involved in the maturation of all cellular iron-sulfur proteins. A mitochondrial export machinery and a recently discovered cytosolic assembly system specifically participate in the maturation of cytosolic and nuclear iron-sulfur proteins. Of the approximately 20 assembly components, more than ten are encoded by essential genes, which indicates that the process is indispensable for life. Mutations in two of the assembly components lead to neurological diseases. The essential character of Fe-S-protein biogenesis in eukaryotes and its importance for human disease identifies this evolutionary ancient process as one of the most important biosynthetic pathways of life.

Animals↗
PubMed2005

Biogenesis of beta-barrel membrane proteins of mitochondria.

beta-Barrel membrane proteins have several important functions in outer membranes of Gram-negative bacteria and in the organelles of endosymbiotic origin, mitochondria and chloroplasts. The biogenesis of beta-barrel membrane proteins was, until recently, an unresolved process. A breakthrough was achieved when a specific pathway for the insertion of beta-barrel outer-membrane proteins was identified in both mitochondria and Gram-negative bacteria. The key component of this pathway is Tob55 (also known as Sam50) in mitochondria and Omp85 in bacteria, both beta-barrel membrane proteins themselves. Tob55 is part of the hetero-oligomeric TOB (topogenesis of mitochondrial outer-membrane beta-barrel proteins) or SAM (sorting and assembly of mitochondria) complex, which is present in the mitochondrial outer membrane. Tob55 belongs to an evolutionarily conserved protein family, the members of which are present in almost all eukaryotes and in Gram-negative bacteria and chloroplasts. Thus, is it emphasized that the insertion pathway of mitochondrial beta-barrel membrane proteins was conserved during evolution of mitochondria from endosymbiotic bacterial ancestors.

Bacterial Proteins↗