Quality control of the mitochondrial proteome Song, Jiyao; Herrmann, Johannes M; Becker, Thomas
Nature reviews. Molecular cell biology,
01/2021, Letnik:
22, Številka:
1
Journal Article
Recenzirano
Mitochondria contain about 1,000-1,500 proteins that fulfil multiple functions. Mitochondrial proteins originate from two genomes: mitochondrial and nuclear. Hence, proper mitochondrial function ...requires synchronization of gene expression in the nucleus and in mitochondria and necessitates efficient import of mitochondrial proteins into the organelle from the cytosol. Furthermore, the mitochondrial proteome displays high plasticity to allow the adaptation of mitochondrial function to cellular requirements. Maintenance of this complex and adaptable mitochondrial proteome is challenging, but is of crucial importance to cell function. Defects in mitochondrial proteostasis lead to proteotoxic insults and eventually cell death. Different quality control systems monitor the mitochondrial proteome. The cytosolic ubiquitin-proteasome system controls protein transport across the mitochondrial outer membrane and removes damaged or mislocalized proteins. Concomitantly, a number of mitochondrial chaperones and proteases govern protein folding and degrade damaged proteins inside mitochondria. The quality control factors also regulate processing and turnover of native proteins to control protein import, mitochondrial metabolism, signalling cascades, mitochondrial dynamics and lipid biogenesis, further ensuring proper function of mitochondria. Thus, mitochondrial protein quality control mechanisms are of pivotal importance to integrate mitochondria into the cellular environment.
Mitochondria contain their own genome that encodes for a small number of proteins, while the vast majority of mitochondrial proteins is produced on cytosolic ribosomes. The formation of respiratory ...chain complexes depends on the coordinated biogenesis of mitochondrially encoded and nuclear-encoded subunits. In this review, we describe pathways that adjust mitochondrial protein synthesis and import of nuclear-encoded subunits to the assembly of respiratory chain complexes. Furthermore, we outline how defects in protein import into mitochondria affect nuclear gene expression to maintain protein homeostasis under physiological and stress conditions.
Corrosion is a subject of interest to interdisciplinary research communities, combining fields of materials science, chemistry, physics, metallurgy and chemical engineering. In order to understand ...mechanisms of corrosion and the function of corrosion inhibitors, the reactions at the interfaces between the corrosive electrolyte and a steel surface, particularly at the initial stages of the corrosion process, need to be described. Naturally, these reactions are strongly affected by the nature and properties of the steel surfaces. It is however seen that the majority of recent corrosion and corrosion-inhibition investigations are limited to electrochemical testing, with
ex situ
analysis of the treated steels (post-exposure analysis). The characterization of materials and their surface properties, such as texture and morphology, are not being considered in most studies. Similarly,
in situ
investigations of the initial stages of the corrosion reactions using advanced surface characterization techniques are scarce. In this review, attention is brought to the importance of surface features of carbon steels, such as texture and surface energy, along with defects dislocation related to mechanical processing of carbon steels. This work is extended to a critical review of surface analytical techniques used for characterization of carbon steels in corrosive media with particular focus on examining steel surfaces treated with corrosion inhibitors. Further, emerging surface analysis techniques and their applicability to analyse carbon steels in corrosive media are discussed. The importance of surface properties is commonly addressed by surface scientists as well as researchers in other chemistry fields such as nanotechnology, fuel cells, and catalysis. This article is expected to appeal to a broad scientific community, including but not limited to corrosion scientists, material chemists, analytical chemists, metal physicists, corrosion and materials engineers.
The effects of surface morphology, defects, texture and energy on carbon steel corrosion are elucidated along with relevant characterization methods.
Mitochondria and chloroplasts import the vast majority of their proteins across two membranes, and use translocases of the outer membrane as an entry gate. These translocases interact with the ...incoming precursor protein and guiding chaperone factors. Within the translocon, precursor-protein receptors dock to a central component that mediates both transfer through a cation-selective channel and initial sorting towards internal subcompartments. Despite these similarities, the mode of translocation differs between the two organelles: in chloroplasts, GTP-binding and hydrolysis by the receptors is required for transport, whereas in mitochondria passage of the preprotein is driven by its increasing affinity for the translocase subunits.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Statistical control is widely used in correlational studies with the intent of providing more accurate estimates of relationships among variables, more conservative tests of hypotheses, or ruling out ...alternative explanations for empirical findings. However, the use of control variables can produce uninterpretable parameter estimates, erroneous inferences, irreplicable results, and other barriers to scientific progress. As a result, methodologists have provided a great deal of advice regarding the use of statistical control, to the point that researchers might have difficulties sifting through and prioritizing the available suggestions. We integrate and condense this literature into a set of 10 essential recommendations that are generally applicable and which, if followed, would substantially enhance the quality of published organizational research. We provide explanations, qualifications, and examples following each recommendation.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current coronavirus disease 2019 (COVID-19) pandemic. A major virulence factor of SARS-CoVs is the ...nonstructural protein 1 (Nsp1), which suppresses host gene expression by ribosome association. Here, we show that Nsp1 from SARS-CoV-2 binds to the 40
ribosomal subunit, resulting in shutdown of messenger RNA (mRNA) translation both in vitro and in cells. Structural analysis by cryo-electron microscopy of in vitro-reconstituted Nsp1-40
and various native Nsp1-40
and -80
complexes revealed that the Nsp1 C terminus binds to and obstructs the mRNA entry tunnel. Thereby, Nsp1 effectively blocks retinoic acid-inducible gene I-dependent innate immune responses that would otherwise facilitate clearance of the infection. Thus, the structural characterization of the inhibitory mechanism of Nsp1 may aid structure-based drug design against SARS-CoV-2.
The author examines statistical control in a random sample of 60 articles published in four top journals during 2000 to 2002. Authors’bases for including control variables, clarity regarding measures ...and methods, and reporting of results were recorded. Potential problems included a lack of explanations for inclusion, unclear descriptions of measures and methods, incomplete reporting, and other flaws. Implications for interpreting results, replication, future reviews, and effect sizes are discussed. Twelve recommendations for addressing these issues are offered.
Spinal cord injury leads to a massive response of innate immune cells in non-regenerating mammals, but also in successfully regenerating zebrafish. However, the role of the immune response in ...successful regeneration is poorly defined. Here we show that inhibiting inflammation reduces and promoting it accelerates axonal regeneration in spinal-lesioned zebrafish larvae. Mutant analyses show that peripheral macrophages, but not neutrophils or microglia, are necessary for repair. Macrophage-less irf8 mutants show prolonged inflammation with elevated levels of Tnf-α and Il-1β. Inhibiting Tnf-α does not rescue axonal growth in irf8 mutants, but impairs it in wildtype animals, indicating a pro-regenerative role of Tnf-α. In contrast, decreasing Il-1β levels or number of Il-1β
neutrophils rescue functional regeneration in irf8 mutants. However, during early regeneration, interference with Il-1β function impairs regeneration in irf8 and wildtype animals. Hence, inflammation is dynamically controlled by macrophages to promote functional spinal cord regeneration in zebrafish.
Mitochondrial biogenesis requires the import of a large number of precursor proteins from the cytosol. Although specific membrane-bound preprotein translocases have been characterized in detail, it ...was assumed that protein transfer from the cytosol to mitochondria mainly involved unselective binding to molecular chaperones. Recent findings suggest an unexpected versatility of protein transfer to mitochondria. Cytosolic factors have been identified that bind to selected subsets of preproteins and guide them to mitochondrial receptors in a post-translational manner. Cotranslational import processes are emerging. Mechanisms for crosstalk between protein targeting to mitochondria and other cell organelles, in particular the endoplasmic reticulum (ER) and peroxisomes, have been uncovered. We discuss how a network of cytosolic machineries and targeting pathways promote and regulate preprotein transfer into mitochondria.
The majority of mitochondrial proteins are targeted to mitochondria upon the completion of protein synthesis at cytosolic ribosomes (post-translational translocation). A network of chaperones, cochaperones, and further cytosolic factors guides preproteins to the translocase of the mitochondrial outer membrane.Cochaperones such as J-proteins provide selectivity for subgroups of mitochondrial preproteins and bind to specific receptors on the mitochondrial surface.mRNAs and cytosolic ribosomes can associate with the mitochondrial outer membrane. Several mitochondrial proteins are imported in a cotranslational manner via association of ribosome–nascent chain complexes with the translocase of the outer membrane.The targeting pathways of some preproteins to mitochondria, ER, and peroxisomes are in functional crosstalk and can share cytosolic factors.The regulation of cytosolic factors and targeting pathways provides a means of adapting organelle biogenesis to metabolism and environmental cues.
Clarification of wheat dough functionalities by visualizing the protein microstructure demands a precise image analysis, which is still challenging. Thus, a novel method for quantifying dough ...microstructure called protein network analysis (PNA) was established in this study. Hereby, absolute morphological attributes such as junctions' density, branching rate, end-point rate, and lacunarity quantify and characterize the strength of a network. The method was validated in a large range of varying microstructural shapes by increasing the bulk water concentration. In addition, the effect of two different magnifications (objectives with various numerical apparatus) was studied. Resulting values of the branching rate showed a significant linear decrease (R2=0.97) by ~40% for both magnifications indicating a decrease in connectivity and cohesion within the network. Rheological measurements, used as reference methods confirmed the loss of a network structure with increasing water addition (e.g. G* decreased by 89%). Additionally, significant correlations between both methods validated the innovative image analysis PNA. With this new approach of image analysis, effects of additives, varying dough ingredients or changing process conditions on gluten network - the most structure-relevant component in wheat dough - can be quantitatively identified, and targeted functionalities can be controlled.
Display omitted
•A novel image analysis for wheat dough was established by protein network analysis.•The strength and cohesion of a network can be quantified by the branching rate.•Branching rate was decreased by 40% with rising water addition (59–90ml/100g flour).•Irregularities and gaps in network formations can be characterized by lacunarity.•Significant correlations between rheological and microstructural attributes
PDF
