- Home
- A-Z Publications
- Annual Review of Biochemistry
- Previous Issues
- Volume 76, 2007
Annual Review of Biochemistry - Volume 76, 2007
Volume 76, 2007
- Preface
-
-
-
Molecular Mechanisms of Antibody Somatic Hypermutation
Vol. 76 (2007), pp. 1–22More LessAbstractFunctional antibody genes are assembled by V-D-J joining and then diversified by somatic hypermutation. This hypermutation results from stepwise incorporation of single nucleotide substitutions into the V gene, underpinning much of antibody diversity and affinity maturation. Hypermutation is triggered by activation-induced deaminase (AID), an enzyme which catalyzes targeted deamination of deoxycytidine residues in DNA. The pathways used for processing the AID-generated U:G lesions determine the variety of base substitutions observed during somatic hypermutation. Thus, DNA replication across the uracil yields transition mutations at C:G pairs, whereas uracil excision by UNG uracil-DNA glycosylase creates abasic sites that can also yield transversions. Recognition of the U:G mismatch by MSH2/MSH6 triggers a mutagenic patch repair in which polymerase eta plays a major role and leads to mutations at A:T pairs. AID-triggered DNA deamination also underpins immunoglobulin variable (IgV) gene conversion, isotype class switching, and some oncogenic translocations in B cell tumors.
-
-
-
Structure and Mechanism of Helicases and Nucleic Acid Translocases
Vol. 76 (2007), pp. 23–50More LessAbstractHelicases and translocases are a ubiquitous, highly diverse group of proteins that perform an extraordinary variety of functions in cells. Consequently, this review sets out to define a nomenclature for these enzymes based on current knowledge of sequence, structure, and mechanism. Using previous definitions of helicase families as a basis, we delineate six superfamilies of enzymes, with examples of crystal structures where available, and discuss these structures in the context of biochemical data to outline our present understanding of helicase and translocase activity. As a result, each superfamily is subdivided, where appropriate, on the basis of mechanistic understanding, which we hope will provide a framework for classification of new superfamily members as they are discovered and characterized.
-
-
-
The Nonsense-Mediated Decay RNA Surveillance Pathway
Vol. 76 (2007), pp. 51–74More LessAbstractNonsense-mediated mRNA decay (NMD) is a quality-control mechanism that selectively degrades mRNAs harboring premature termination (nonsense) codons. If translated, these mRNAs can produce truncated proteins with dominant-negative or deleterious gain-of-function activities. In this review, we describe the molecular mechanism of NMD. We first cover conserved factors known to be involved in NMD in all eukaryotes. We then describe a unique protein complex that is deposited on mammalian mRNAs during splicing, which defines a stop codon as premature. Interaction between this exon-junction complex (EJC) and NMD factors assembled at the upstream stop codon triggers a series of steps that ultimately lead to mRNA decay. We discuss whether these proofreading events preferentially occur during a “pioneer” round of translation in higher and lower eukaryotes, their cellular location, and whether they can use alternative EJC factors or act independent of the EJC.
-
-
-
Functions of Site-Specific Histone Acetylation and Deacetylation
Vol. 76 (2007), pp. 75–100More LessAbstractHistone acetylation regulates many cellular processes, and specific acetylation marks, either singly or in combination, produce distinct outcomes. For example, the acetylation pattern on newly synthesized histones is important for their assembly into nucleosomes by histone chaperones. Additionally, the degree of chromatin compaction and folding may be regulated by acetylation of histone H4 at lysine 16. Histone acetylation also regulates the formation of heterochromatin; deacetylation of H4 lysine 16 is important for spreading of heterochromatin components, whereas acetylation of this site serves as a barrier to this spreading. Finally, histone acetylation is critical for gene transcription, but recent results suggest that deacetylation of certain sites also plays an important role. There are many histone acetyltransferases (HATs) and deacetylases, with differing preferences for the various histone proteins and for specific sites on individual histones. Determining how these enzymes create distinct acetylation patterns and regulate the functional outcome is an important challenge.
-
-
-
The tmRNA System for Translational Surveillance and Ribosome Rescue
Vol. 76 (2007), pp. 101–124More LessAbstractThe tmRNA system performs translational surveillance and ribosome rescue in all eubacteria and some eukaryotic organelles. This system intervenes when ribosomes read to the 3′ end of an mRNA or pause at internal codons with subsequent mRNA cleavage. A complex of alanyl-tmRNA (which functions as a tRNA and mRNA), SmpB protein, and EF-Tu•GTP binds stalled ribosomes, the nascent polypeptide is transferred to the alanine on tmRNA, and translation switches from the original message to a short tmRNA open reading frame (ORF) that encodes a degradation tag. Translation of the ORF and normal termination releases the tagged polypeptide for degradation and permits disassembly and recycling of ribosomal subunits for new rounds of protein synthesis. Structural and biochemical studies suggest mechanisms that keep tmRNA from interrupting normal translation and target ribosomes stalled with very short 3′ mRNA extensions. Additional biological roles of tmRNA include stress management and the regulation of transcriptional circuits.
-
-
-
Membrane Protein Structure: Prediction versus Reality
Vol. 76 (2007), pp. 125–140More LessAbstractSince high-resolution structural data are still scarce, different kinds of theoretical structure prediction algorithms are of major importance in membrane protein biochemistry. But how well do the current prediction methods perform? Which structural features can be predicted and which cannot? And what can we expect in the next few years?
-
-
-
Structure and Function of Toll Receptors and Their Ligands
Vol. 76 (2007), pp. 141–165More LessAbstractThe Toll family of class I transmembrane receptors recognizes and responds to diverse structures associated with pathogenic microorganisms. These receptors mediate initial responses in innate immunity and are required for the development of the adaptive immune response. Toll receptor signaling pathways are also implicated in serious autoimmune diseases such as endotoxic shock and thus are important therapeutic targets. In this review we discuss how microbial structures as different as nucleic acids and lipoproteins can be recognized by the extracellular domains of Toll receptors. We review recent evidence that the mechanism of signal transduction is complex and involves sequential changes in the conformation of the receptor induced by binding of the ligand. Finally, we assess the emerging area of cross talk in the Toll pathways. Recent work suggests that signaling through TLR4 in response to endotoxin is modified by inputs from at least two other pathways acting through β2 integrins and protein kinase Cε.
-
-
-
The Role of Mass Spectrometry in Structure Elucidation of Dynamic Protein Complexes
Vol. 76 (2007), pp. 167–193More LessAbstractThe fact that ions of macromolecular complexes produced by electrospray ionization can be maintained intact in a mass spectrometer has stimulated exciting new lines of research. In this review we chart the progress of this research from the observation of simple homo-oligomers to complex heterogeneous macromolecular assemblies of mega-Dalton proportions. The applications described herein not only confirm the status of mass spectrometry (MS) as a structural biology approach to complement X-ray analysis or electron microscopy, but also highlight unique attributes of the methodology. This is exemplified in studies of the biogenesis of macromolecular complexes and in the exchange of subunits between macromolecular complexes. Moreover, recent successes in revealing the overall subunit architecture of complexes are set to promote MS from a complementary approach to a structural biology tool in its own right.
-
-
-
Structure and Mechanism of the 6-Deoxyerythronolide B Synthase
Vol. 76 (2007), pp. 195–221More LessAbstract6-Deoxyerythronolide B, the macrocyclic aglycone of the antibiotic erythromycin, is synthesized by a polyketide synthase (PKS) that has emerged as the prototypical modular megasynthase. A variety of molecular biological, protein chemical, and biosynthetic experiments over the past two decades have yielded insights into its mechanistic features. More recently, high-resolution structural images of portions of the 6-deoxyerythronolide B synthase have provided a platform for interpreting this wealth of biochemical data, while at the same time presenting a fundamentally new basis for the design of more detailed investigations into this remarkable enzyme. For example, the critical roles of domain-domain interactions and nonconserved linkers, as well as large interdomain movements in the structure and function of modular PKSs, have been highlighted. In turn, these insights point the way forward for more sophisticated and efficient biosynthetic engineering of complex polyketide natural products.
-
-
-
The Biochemistry of Methane Oxidation
Vol. 76 (2007), pp. 223–241More LessAbstractMethanotrophic bacteria oxidize methane to methanol in the first step of their metabolic pathway. Two forms of methane monooxygenase (MMO) enzymes catalyze this reaction: soluble MMO (sMMO) and membrane-bound or particulate MMO (pMMO). pMMO is expressed when copper is available, and its active site is believed to contain copper. Whereas sMMO is well characterized, most aspects of pMMO biochemistry remain unknown and somewhat controversial. This review emphasizes advances in the past two to three years related to pMMO and to copper uptake and copper-dependent regulation in methanotrophs. The pMMO metal centers have been characterized spectroscopically, and the first pMMO crystal structure has been determined. Significant effort has been devoted to improving in vitro pMMO activity. Proteins involved in sMMO regulation and additional copper-regulated proteins have been identified, and the Methylococcus capsulatus (Bath) genome has been sequenced. Finally, methanobactin (mb), a small copper chelator proposed to facilitate copper uptake, has been characterized.
-
-
-
Anthrax Toxin: Receptor Binding, Internalization, Pore Formation, and Translocation
Vol. 76 (2007), pp. 243–265More LessAbstractAnthrax toxin consists of three nontoxic proteins that self-assemble at the surface of receptor-bearing mammalian cells or in solution, yielding a series of toxic complexes. Two of the proteins, called Lethal Factor (LF) and Edema Factor (EF), are enzymes that act on cytosolic substrates. The third, termed Protective Antigen (PA), is a multifunctional protein that binds to receptors, orchestrates the assembly and internalization of the complexes, and delivers them to the endosome. There, the PA moiety forms a pore in the endosomal membrane and promotes translocation of LF and EF to the cytosol. Recent advances in understanding the entry process include insights into how PA recognizes its two known receptors and its ligands, LF and EF; how the PA:receptor interaction influences the pH-dependence of pore formation; and how the pore functions in promoting translocation of LF and EF across the endosomal membrane.
-
-
-
Synapses: Sites of Cell Recognition, Adhesion, and Functional Specification
Vol. 76 (2007), pp. 267–294More LessAbstractSynapses are specialized adhesive contacts characteristic of many types of cell-cell interactions involving neurons, immune cells, epithelial cells, and even pathogens and host cells. Cell-cell adhesion is mediated by structurally diverse classes of cell-surface glycoproteins, which form homophilic or heterophilic interactions across the intercellular space. Adhesion proteins bind to a cytoplasmic network of scaffolding proteins, regulators of the actin cytoskeleton, and signal transduction pathways that control the structural and functional organization of synapses. The themes of this review are to compare the organization of synapses in different cell types and to understand how different classes of cell adhesion proteins and cytoplasmic protein networks specify the assembly of functionally distinct synapses in different cell contexts.
-
-
-
Lipid A Modification Systems in Gram-Negative Bacteria
Vol. 76 (2007), pp. 295–329More LessAbstractThe lipid A moiety of lipopolysaccharide forms the outer monolayer of the outer membrane of most gram-negative bacteria. Escherichia coli lipid A is synthesized on the cytoplasmic surface of the inner membrane by a conserved pathway of nine constitutive enzymes. Following attachment of the core oligosaccharide, nascent core-lipid A is flipped to the outer surface of the inner membrane by the ABC transporter MsbA, where the O-antigen polymer is attached. Diverse covalent modifications of the lipid A moiety may occur during its transit from the outer surface of the inner membrane to the outer membrane. Lipid A modification enzymes are reporters for lipopolysaccharide trafficking within the bacterial envelope. Modification systems are variable and often regulated by environmental conditions. Although not required for growth, the modification enzymes modulate virulence of some gram-negative pathogens. Heterologous expression of lipid A modification enzymes may enable the development of new vaccines.
-
-
-
Chemical Evolution as a Tool for Molecular Discovery
Vol. 76 (2007), pp. 331–349More LessAbstractIn modern academic and industrial laboratories, evolutionary strategies are used routinely to identify biopolymers with novel activities. Large libraries of nucleic acids (∼1015) or peptides and proteins (∼1013) can be subjected to multiple rounds of selective pressure, amplification, and diversification, yielding individual sequences with desirable properties. Although the evolutionary approach is a powerful search tool, the chemical nature of biopolymers is not suited for all purposes. Application of evolutionary strategies to libraries of arbitrary chemical composition would overcome this problem, and radically change traditional small-molecule discovery. The chemical make-up of in vitro evolution libraries has necessarily been limited, because library synthesis relies on enzymes. A great deal of current research focuses on expanding the chemical repertoire of in vitro evolution by (a) broadening enzyme substrate specificities to include unnatural building blocks, or (b) developing methods to translate DNA sequences into multistep organic syntheses. We discuss the strengths and weaknesses of the approaches, review the successes, and consider the future of chemical evolution as a tool.
-
-
-
Molecular Mechanisms of Magnetosome Formation
Vol. 76 (2007), pp. 351–366More LessAbstractMagnetotactic bacteria are a diverse group of microorganisms with the ability to use geomagnetic fields for direction sensing. This unique feat is accomplished with the help of magnetosomes, nanometer-sized magnetic crystals surrounded by a lipid bilayer membrane and organized into chains via a dedicated cytoskeleton within the cell. Because of the special properties of these magnetic crystals, magnetotactic bacteria have been exploited for a variety of applications in diverse disciplines from geobiology to biotechnology. In addition, magnetosomes have served as a powerful model system for the study of biomineralization and cell biology in bacteria. This review focuses on recent advances in understanding the molecular mechanisms of magnetosome formation and magnetite biomineralization.
-
-
-
Modulation of the Ryanodine Receptor and Intracellular Calcium
Vol. 76 (2007), pp. 367–385More LessAbstractRyanodine receptors (RyRs)/Ca2+ release channels, on the endoplasmic and sarcoplasmic reticulum of most cell types, are required for intracellular Ca2+ release involved in diverse cellular functions, including muscle contraction and neurotransmitter release. The large cytoplasmic domain of the RyR serves as a scaffold for proteins that bind to and modulate the channel's function and that comprise a macromolecular signaling complex. These proteins include calstabins [FK506-binding proteins (FKBPs)], calmodulin (CaM), phosphodiesterase, kinases, phosphatases, and their cognate targeting proteins. This review focuses on recent progress in the understanding of RyR regulation and disease mechanisms that are associated with channel dysfunction.
-
-
-
TRP Channels
Vol. 76 (2007), pp. 387–417More LessAbstractThe TRP (Transient Receptor Potential) superfamily of cation channels is remarkable in that it displays greater diversity in activation mechanisms and selectivities than any other group of ion channels. The domain organizations of some TRP proteins are also unusual, as they consist of linked channel and enzyme domains. A unifying theme in this group is that TRP proteins play critical roles in sensory physiology, which include contributions to vision, taste, olfaction, hearing, touch, and thermo- and osmosensation. In addition, TRP channels enable individual cells to sense changes in their local environment. Many TRP channels are activated by a variety of different stimuli and function as signal integrators. The TRP superfamily is divided into seven subfamilies: the five group 1 TRPs (TRPC, TRPV, TRPM, TRPN, and TRPA) and two group 2 subfamilies (TRPP and TRPML). TRP channels are important for human health as mutations in at least four TRP channels underlie disease.
-
-
-
Studying Individual Events in Biology
Vol. 76 (2007), pp. 419–446More LessAbstractStudying the properties of individual events and molecules offers a host of advantages over taking only macroscopic measurements of populations. Here we review such advantages, as well as some pitfalls, focusing on examples from biological imaging. Examples include single proteins, their interactions in cells, organelles, and their interactions both with each other and with parts of the cell. Additionally, we discuss constraints that limit the study of single events, along with the criteria that must be fulfilled to determine whether single molecules or events are being detected.
-
-
-
Signaling Pathways Downstream of Pattern-Recognition Receptors and Their Cross Talk
Vol. 76 (2007), pp. 447–480More LessAbstractPattern-recognition receptors (PRRs) initiate innate immunity through pathogen recognition. Serum PRRs opsonize pathogens for enhanced phagocytic clearance. Toll-like receptors (TLRs) initiate common NF-κB/AP-1 and distinct IRF3/7 pathways to coordinate innate immunity and to initiate adaptive immunity against diverse pathogens. Cytoplasmic caspase-recruiting domain (CARD) helicases, such as RIG-I/MDA5, mediate antiviral immunity by inducing the production of type I interferons via the adaptor IPS-1, whereas nucleotide-binding oligomerization domain (NOD)-like receptors mediate mainly antibacterial immunity by activating NF-κB or inflammasomes. Dectin-1 is important for antifungal immunity, promoting phagocytosis and activating NF-κB. Potentially harmful TLR signaling pathways can be negatively regulated by negative feedback mechanisms and also by anti-inflammatory factors such as TGFβ, interleukin (IL)-10, and steroids. Many combinations of TLR-TLR and TLR-NOD modulate inflammatory responses. TLRs and NALP3 interplay to produce mature IL-1β. Thus signaling pathways downstream of PRRs and their cross talk control immune responses in effective manners.
-
-
-
Biochemistry and Physiology of Cyclic Nucleotide Phosphodiesterases: Essential Components in Cyclic Nucleotide Signaling
Marco Conti, and Joseph BeavoVol. 76 (2007), pp. 481–511More LessAbstractAlthough cyclic nucleotide phosphodiesterases (PDEs) were described soon after the discovery of cAMP, their complexity and functions in signaling is only recently beginning to become fully realized. We now know that at least 100 different PDE proteins degrade cAMP and cGMP in eukaryotes. A complex PDE gene organization and a large number of PDE splicing variants serve to fine-tune cyclic nucleotide signals and contribute to specificity in signaling. Here we review some of the major concepts related to our understanding of PDE function and regulation including: (a) the structure of catalytic and regulatory domains and arrangement in holoenzymes; (b) PDE integration into signaling complexes; (c) the nature and function of negative and positive feedback circuits that have been conserved in PDEs from prokaryotes to human; (d) the emerging association of mutant PDE alleles with inherited diseases; and (e) the role of PDEs in generating subcellular signaling compartments.
-
-
-
The Eyes Absent Family of Phosphotyrosine Phosphatases: Properties and Roles in Developmental Regulation of Transcription
Vol. 76 (2007), pp. 513–538More LessAbstractIntegration of multiple signaling pathways at the level of their transcriptional effectors provides an important strategy for fine-tuning gene expression and ensuring a proper program of development. Posttranslational modifications, such as phosphorylation, play important roles in modulating transcription factor activity. The discovery that the transcription factor Eyes absent (Eya) possesses protein phosphatase activity provides an interesting new paradigm. Eya may regulate the phosphorylation state of either itself or its transcriptional cofactors, thereby directly affecting transcriptional output. The identification of a growing number of transcription factors with enzymic activity suggests that such dual-function proteins exert greater control of signaling events than previously imagined. Given the conservation of both its phosphatase and transcription factor activity across mammalian species, Eya provides an excellent model for studying how a single protein integrates these two functions under the influence of multiple signaling pathways to promote development.
-
-
-
Assembly Dynamics of the Bacterial MinCDE System and Spatial Regulation of the Z Ring
Vol. 76 (2007), pp. 539–562More LessAbstractThe positioning of a cytoskeletal element that dictates the division plane is a fundamental problem in biology. The assembly and positioning of this cytoskeletal element has to be coordinated with DNA segregation and cell growth to ensure that equal-sized progeny cells are produced, each with a copy of the chromosome. In most prokaryotes, cytokinesis involves positioning a Z ring assembled from FtsZ, the ancestral homologue of tubulin. The position of the Z ring is determined by a gradient of negative regulators of Z-ring assembly. In Escherichia coli, the Min system consists of three proteins that cooperate to position the Z ring through a fascinating oscillation, which inhibits the formation of the Z ring away from midcell. Additional gradients of negative regulators of FtsZ assembly are used by E. coli and other bacteria to achieve spatial control of Z-ring assembly.
-
-
-
Structures and Functions of Yeast Kinetochore Complexes
Vol. 76 (2007), pp. 563–591More LessAbstractThe kinetochore is a key cell division organelle that enables high-fidelity transmission of genetic information by coupling chromosomes to spindle microtubules during mitosis and meiosis. Despite its cytological description more than a century ago, remarkably little information is available on kinetochore function at a molecular level. Recently, important advances elucidating the overall organization of kinetochores, as well as information about the structures and molecular mechanisms of kinetochore function, have been achieved through a detailed analysis of the kinetochores of the budding yeast Saccharomyces cerevisiae. Here we review the current understanding of kinetochore function in budding yeast and draw comparisons to recent findings in other organisms.
-
-
-
Mechanism and Function of Formins in the Control of Actin Assembly
Vol. 76 (2007), pp. 593–627More LessAbstractFormins are a widely expressed family of proteins that govern cell shape, adhesion, cytokinesis, and morphogenesis by remodeling the actin and microtubule cytoskeletons. These large multidomain proteins associate with a variety of other cellular factors and directly nucleate actin polymerization through a novel mechanism. The signature formin homology 2 (FH2) domain initiates filament assembly and remains persistently associated with the fast-growing barbed end, enabling rapid insertion of actin subunits while protecting the end from capping proteins. On the basis of structural and mechanistic work, an integrated model is presented for FH2 processive motion. The adjacent FH1 domain recruits profilin-actin complexes and accelerates filament elongation. The most predominantly expressed formins in animals and fungi are autoinhibited through intramolecular interactions and appear to be activated by Rho GTPases and additional factors. Other classes of formins lack the autoinhibitory and/or Rho-binding domains and thus are likely to be controlled by alternative mechanisms.
-
-
-
Unsolved Mysteries in Membrane Traffic
Vol. 76 (2007), pp. 629–645More LessAbstractRemarkable strides have been made over the past 20 years in elucidating the molecular basis of membrane trafficking (1). Indeed, a combination of biochemical and genetic approaches have determined the identity and function of many of the core constituents needed for protein secretion and endocytosis. But much remains to be learned. This review highlights underlying themes in membrane traffic to help us refocus and solve many remaining and newly emerging issues that are fundamental to mammalian cell biology and human physiology.
-
-
-
Structural Biology of Nucleocytoplasmic Transport
Vol. 76 (2007), pp. 647–671More LessAbstractIn eukaryotic cells, segregation of DNA replication and RNA biogenesis in the nucleus and protein synthesis in the cytoplasm poses the requirement of transporting thousands of macromolecules between the two cellular compartments. Transport between nucleus and cytoplasm is mediated by soluble receptors that recognize specific cargoes and carry them through the nuclear pore complex (NPC), the sole gateway between the two compartments at interphase. Nucleocytoplasmic transport is specific not only in terms of cargo recognition, but also in terms of directionality, with nuclear proteins imported into the nucleus and RNAs exported from it. How is directionality achieved? How can the receptors be both specific and versatile in recognizing a multitude of cargoes? And how can their interaction with NPCs allow fast translocation? We describe the molecular mechanisms underlying nucleocytoplasmic transport as they have been revealed by structural studies of the receptors and regulators in different steps of transport cycles.
-
-
-
The Magic Garden
Vol. 76 (2007), pp. 673–678More LessAbstractFor more than a century after their discovery, mitochondria were viewed almost exclusively as ATP-generating metabolic units. This view changed with the discovery of the mitochondrial genetic system and the central role of mitochondria in programmed cell death. As a result, much of the current research focuses on the complex interplay between mitochondria and the rest of the eukaryotic cell. This interplay is central to mitochondrial biogenesis. The following five reviews published in this volume summarize recent discoveries in this area: DNA Replication and Transcription in Mammalian Mitochondria, Mitochondrial-Nuclear Communications, Translocation of Proteins into Mitochondria, The Machines that Divide and Fuse Mitochondria, and Why Do We Still Have a Maternally Inherited Mitochondrial DNA? Insights from Evolutionary Medicine.
-
-
-
DNA Replication and Transcription in Mammalian Mitochondria
Vol. 76 (2007), pp. 679–699More LessAbstractThe mitochondrion was originally a free-living prokaryotic organism, which explains the presence of a compact mammalian mitochondrial DNA (mtDNA) in contempory mammalian cells. The genome encodes for key subunits of the electron transport chain and RNA components needed for mitochondrial translation. Nuclear genes encode the enzyme systems responsible for mtDNA replication and transcription. Several of the key components of these systems are related to proteins replicating and transcribing DNA in bacteriophages. This observation has led to the proposition that some genes required for DNA replication and transcription were acquired together from a phage early in the evolution of the eukaryotic cell, already at the time of the mitochondrial endosymbiosis. Recent years have seen a rapid development in our molecular understanding of these machineries, but many aspects still remain unknown.
-
-
-
Mitochondrial-Nuclear Communications
Vol. 76 (2007), pp. 701–722More LessAbstractMitochondria cannot be made de novo but replicate by a mechanism of recruitment of new proteins, which are added to preexisting subcompartments. Although mitochondria have their own DNA, more than 98% of the total protein complement of the organelle is encoded by the nuclear genome. Mitochondrial biogenesis requires a coordination of expression of two genomes and therefore cross talk between the nucleus and mitochondria. In mammals, regulation of mitochondrial biogenesis and proliferation is influenced by external factors, such as nutrients, hormones, temperature, exercise, hypoxia, and aging. This complexity points to the existence of a coordinated and tightly regulated network connecting different pathways. Communications are also required for eliciting mitochondrial responses to specific stress pathways. This review covers the mechanisms of mitochondrial biogenesis and the way cells respond to external signals to maintain mitochondrial function and cellular homeostasis.
-
-
-
Translocation of Proteins into Mitochondria
Vol. 76 (2007), pp. 723–749More LessAbstractAbout 10% to 15% of the nuclear genes of eukaryotic organisms encode mitochondrial proteins. These proteins are synthesized in the cytosol and recognized by receptors on the surface of mitochondria. Translocases in the outer and inner membrane of mitochondria mediate the import and intramitochondrial sorting of these proteins; ATP and the membrane potential are used as energy sources. Chaperones and auxilliary factors assist in the folding and assembly of mitochondrial proteins into their native, three-dimensional structures. This review summarizes the present knowledge on the import and sorting of mitochondrial precursor proteins, with a special emphasis on unresolved questions and topics of current research.
-
-
-
The Machines that Divide and Fuse Mitochondria
Vol. 76 (2007), pp. 751–780More LessAbstractMitochondria are derived from eubacteria; however, in most eukaryotes, novel mechanisms for the propagation of this organelle and its genome have evolved. This review focuses on what is currently known about the novel molecular machines that divide and fuse mitochondria.
-
-
-
Why Do We Still Have a Maternally Inherited Mitochondrial DNA? Insights from Evolutionary Medicine
Vol. 76 (2007), pp. 781–821More LessAbstractThe human cell is a symbiosis of two life forms, the nucleus-cytosol and the mitochondrion. The nucleus-cytosol emphasizes structure and its genes are Mendelian, whereas the mitochondrion specializes in energy and its mitochondrial DNA (mtDNA) genes are maternal. Mitochondria oxidize calories via oxidative phosphorylation (OXPHOS) to generate a mitochondrial inner membrane proton gradient (ΔP). ΔP then acts as a source of potential energy to produce ATP, generate heat, regulate reactive oxygen species (ROS), and control apoptosis, etc. Interspecific comparisons of mtDNAs have revealed that the mtDNA retains a core set of electron and proton carrier genes for the proton-translocating OXPHOS complexes I, III, IV, and V. Human mtDNA analysis has revealed these genes frequently contain region-specific adaptive polymorphisms. Therefore, the mtDNA with its energy controlling genes may have been retained to permit rapid adaptation to new environments.
-
-
-
The Postsynaptic Architecture of Excitatory Synapses: A More Quantitative View
Vol. 76 (2007), pp. 823–847More LessAbstractExcitatory (glutamatergic) synapses in the mammalian brain are usually situated on dendritic spines, a postsynaptic microcompartment that also harbors organelles involved in protein synthesis, membrane trafficking, and calcium metabolism. The postsynaptic membrane contains a high concentration of glutamate receptors, associated signaling proteins, and cytoskeletal elements, all assembled by a variety of scaffold proteins into an organized structure called the postsynaptic density (PSD). A complex machine made of hundreds of distinct proteins, the PSD dynamically changes its structure and composition during development and in response to synaptic activity. The molecular size of the PSD and the stoichiometry of many major constituents have been recently measured. The structures of some intact PSD proteins, as well as the spatial arrangement of several proteins within the PSD, have been determined at low resolution by electron microscopy. On the basis of such studies, a more quantitative and geometrically realistic view of PSD architecture is emerging.
-
Previous Volumes
-
Volume 92 (2023)
-
Volume 91 (2022)
-
Volume 90 (2021)
-
Volume 89 (2020)
-
Volume 88 (2019)
-
Volume 87 (2018)
-
Volume 86 (2017)
-
Volume 85 (2016)
-
Volume 84 (2015)
-
Volume 83 (2014)
-
Volume 82 (2013)
-
Volume 81 (2012)
-
Volume 80 (2011)
-
Volume 79 (2010)
-
Volume 78 (2009)
-
Volume 77 (2008)
-
Volume 76 (2007)
-
Volume 75 (2006)
-
Volume 74 (2005)
-
Volume 73 (2004)
-
Volume 72 (2003)
-
Volume 71 (2002)
-
Volume 70 (2001)
-
Volume 69 (2000)
-
Volume 68 (1999)
-
Volume 67 (1998)
-
Volume 66 (1997)
-
Volume 65 (1996)
-
Volume 64 (1995)
-
Volume 63 (1994)
-
Volume 62 (1993)
-
Volume 61 (1992)
-
Volume 60 (1991)
-
Volume 59 (1990)
-
Volume 58 (1989)
-
Volume 57 (1988)
-
Volume 56 (1987)
-
Volume 55 (1986)
-
Volume 54 (1985)
-
Volume 53 (1984)
-
Volume 52 (1983)
-
Volume 51 (1982)
-
Volume 50 (1981)
-
Volume 49 (1980)
-
Volume 48 (1979)
-
Volume 47 (1978)
-
Volume 46 (1977)
-
Volume 45 (1976)
-
Volume 44 (1975)
-
Volume 43 (1974)
-
Volume 42 (1973)
-
Volume 41 (1972)
-
Volume 40 (1971)
-
Volume 39 (1970)
-
Volume 38 (1969)
-
Volume 37 (1968)
-
Volume 36 (1967)
-
Volume 35 (1966)
-
Volume 34 (1965)
-
Volume 33 (1964)
-
Volume 32 (1963)
-
Volume 31 (1962)
-
Volume 30 (1961)
-
Volume 29 (1960)
-
Volume 28 (1959)
-
Volume 27 (1958)
-
Volume 26 (1957)
-
Volume 25 (1956)
-
Volume 24 (1955)
-
Volume 23 (1954)
-
Volume 22 (1953)
-
Volume 21 (1952)
-
Volume 20 (1951)
-
Volume 19 (1950)
-
Volume 18 (1949)
-
Volume 17 (1948)
-
Volume 16 (1947)
-
Volume 15 (1946)
-
Volume 14 (1945)
-
Volume 13 (1944)
-
Volume 12 (1943)
-
Volume 11 (1942)
-
Volume 10 (1941)
-
Volume 9 (1940)
-
Volume 8 (1939)
-
Volume 7 (1938)
-
Volume 6 (1937)
-
Volume 5 (1936)
-
Volume 4 (1935)
-
Volume 3 (1934)
-
Volume 2 (1933)
-
Volume 1 (1932)
-
Volume 0 (1932)