This paper presents a parallel Eulerian/Lagrangian multi-scale coupling procedure for two-phase flows. At the fully resolved scale, the dynamically evolving phase interface is tracked using a ...Eulerian approach. In regions of the flow, where the phase interface geometry can no longer be resolved adequately, separated, small scale liquid structures are described by a Lagrangian point particle approach. The coupling procedure of these two descriptions consists of an efficient parallel algorithm that identifies tracked liquid candidate structures, removes them from the resolved Eulerian description, and inserts them into the Lagrangian description preserving their position, mass, momentum, and lower order shape. While in principle applicable to level set, Volume of Fluid, and marker particle interface tracking methods for the fully resolved scale, this paper focuses on examples from atomization simulations using the refined level set grid method.
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.
A balanced force refined level set grid method for two-phase flows on structured and unstructured flow solver grids is presented. To accurately track the phase interface location, an auxiliary, ...high-resolution equidistant Cartesian grid is introduced. In conjunction with a dual-layer narrow band approach, this refined level set grid method allows for parallel, efficient grid convergence and error estimation studies of the interface tracking method. The Navier–Stokes equations are solved on an unstructured flow solver grid with a novel balanced force algorithm for level set methods based on the recently proposed method by Francois et al. M.M. Francois, S.J. Cummins, E.D. Dendy, D.B. Kothe, J.M. Sicilian, M.W. Williams, A balanced-force algorithm for continuous and sharp interfacial surface tension models within a volume tracking framework, J. Comput. Phys. 213 (2006) 141–173 for volume of fluid methods on structured grids. To minimize spurious currents, a second order converging curvature evaluation technique for level set methods is presented. The results of several different test cases demonstrate the effectiveness of the proposed method, showing good mass conservation properties and second order converging spurious current magnitudes.
This paper presents a novel model for the sub-filter surface tension induced motion of interfaces separating immiscible fluids. A key feature of the proposed Sub-Grid Surface Dynamics (SGSD) model is ...to take the sub-filter interface dynamics fully into account by employing a dual-scale approach. Instead of modeling the sub-filter interface geometry, it is resolved on an auxiliary grid using the Refined Level Set Grid approach. The required sub-filter velocity field on the auxiliary grid is reconstructed solving a PDE in a narrow band surrounding the interface. With the fully resolved interface geometry available, the previously unclosed surface tension term in the filtered Navier–Stokes equations can be directly closed using explicit filtering. The novel model shows excellent results for different test cases, including sub-grid oscillations of drops, the sub-grid Rayleigh–Plateau instability, and the viscous capillary breakup of a ligament.
Two multisubunit protein complexes for membrane protein insertion were recently identified in the endoplasmic reticulum (ER): the guided entry of tail anchor proteins (GET) complex and ER membrane ...complex (EMC). The structures of both of their hydrophobic core subunits, which are required for the insertion reaction, revealed an overall similarity to the YidC/Oxa1/Alb3 family members found in bacteria, mitochondria, and chloroplasts. This suggests that these membrane insertion machineries all share a common ancestry. To test whether these ER proteins can functionally replace Oxa1 in yeast mitochondria, we generated strains that express mitochondria-targeted Get2-Get1 and Emc6-Emc3 fusion proteins in Oxa1 deletion mutants. Interestingly, the Emc6-Emc3 fusion was able to complement an Δoxa1 mutant and restored its respiratory competence. The Emc6-Emc3 fusion promoted the insertion of the mitochondrially encoded protein Cox2, as well as of nuclear encoded inner membrane proteins, although was not able to facilitate the assembly of the Atp9 ring. Our observations indicate that protein insertion into the ER is functionally conserved to the insertion mechanism in bacteria and mitochondria and adheres to similar topological principles.
In this paper, we study the impact of density ratio on turbulent liquid jet in crossflow penetration and atomization if all other characteristic parameters, i.e., momentum flux ratio, jet and ...crossflow Weber and Reynolds numbers, are maintained constant. We perform detailed simulations of the primary atomization region using the refined level set grid method to track the motion of the liquid/gas phase interface. We employ a balanced force, interface projected curvature method to ensure high accuracy of the surface tension forces, use a multi-scale approach to transfer broken-off, small scale nearly spherical drops into a Lagrangian point particle description allowing for full two-way coupling and continued secondary atomization, and employ a dynamic Smagorinsky large eddy simulation approach in the single phase regions of the flow to describe turbulence. We compare simulation results obtained previously using a liquid to gas density ratio of 10 for a momentum flux ratio 6.6, Weber number 330, and Reynolds number 14,000 liquid jet injected into a Reynolds number 740,000 gaseous crossflow to those at a density ratio of 100, a value typical for gas turbine combustors. The results show that the increase in density ratio results in a noticeable increase in jet penetration, change in drop size distribution resulting from primary atomization, change in drop velocities generated by primary atomization in the crossflow and jet direction, but virtually no change in drop velocities in the transverse direction.
While targeting of proteins synthesized in the cytosol to any organelle is complex, mitochondria present the most challenging of destinations. First, import of nuclear-encoded proteins needs to be ...balanced with production of mitochondrial-encoded ones. Moreover, as mitochondria are divided into distinct subdomains, their proteins harbor a number of different targeting signals and biophysical properties. While translocation into the mitochondrial membranes has been well studied, the cytosolic steps of protein import remain poorly understood. Here, we review current knowledge on mRNA and protein targeting to mitochondria, as well as recent advances in our understanding of the cellular programs that respond to accumulation of mitochondrial precursor proteins in the cytosol, thus linking defects in targeting-capacity to signaling.
Mitochondrial proteins synthetized in the cytosol can be targeted to mitochondria at different stages of gene expression: as mRNAs, ribosome-nascent chain complexes, or complete precursor proteins.While almost all proteins use the same entry gate to the mitochondria, before and after it they can embark on different targeting and import pathways.Delays in mitochondrial protein import or mistargeting to other organelles affect cellular homeostasis; hence, cells have evolved specific mechanisms to sense and counteract such situations.Cytosolic chaperones promote mitochondrial protein import under normal conditions, as well as play a major role in stress response pathways associated with mitochondrial protein import defects.
Mitochondrial and cytosolic proteostasis are of central relevance for cellular stress resistance and organismal health. Recently, a number of individual cellular programs were described that counter ...the fatal consequences of mitochondrial dysfunction. These programs remove arrested import intermediates from mitochondrial protein translocases, stabilize protein homeostasis within mitochondria, and, in particular, increase the levels and activity of chaperones and the proteasome system in the cytosol. Here, we describe the different responses to mitochondrial perturbation and propose to unify the seemingly distinct mitochondrial-cytosolic quality control mechanisms into a single network, the mitoprotein-induced stress response. This holistic view places mitochondrial biogenesis at a central position of the cellular proteostasis network, emphasizing the importance of mitochondrial protein import processes for development, reproduction, and ageing.
Owing to their post-translational mode of import, mitochondrial precursor proteins represent a significant challenge to the cells’ ability to maintain cytosolic proteostasis, particularly when the amount of cytosolic precursors exceeds the import capacity of mitochondria.Mitoprotein-induced stress elicits a complex regulatory network that: (i) removes stalled precursors from the mitochondrial surface, (ii) slows down the synthesis of mitochondrial proteins, and (iii) increases the levels of chaperones and proteases and attenuates cytosolic translation.Seemingly disparate reactions to mitochondrial stress are integrated into a general mitoprotein-induced stress response that couples ‘mitochondria-centric’ adaptations with general stress programs such as the heat shock response.
Apoptosis is an evolutionarily conserved and tightly regulated cell death modality. It serves important roles in physiology by sculpting complex tissues during embryogenesis and by removing effete ...cells that have reached advanced age or whose genomes have been irreparably damaged. Apoptosis culminates in the rapid and decisive removal of cell corpses by efferocytosis, a term used to distinguish the engulfment of apoptotic cells from other phagocytic processes. Over the past decades, the molecular and cell biological events associated with efferocytosis have been rigorously studied, and many eat-me signals and receptors have been identified. The externalization of phosphatidylserine (PS) is arguably the most emblematic eat-me signal that is in turn bound by a large number of serum proteins and opsonins that facilitate efferocytosis. Under physiological conditions, externalized PS functions as a dominant and evolutionarily conserved immunosuppressive signal that promotes tolerance and prevents local and systemic immune activation. Pathologically, the innate immunosuppressive effect of externalized PS has been hijacked by numerous viruses, microorganisms, and parasites to facilitate infection, and in many cases, establish infection latency. PS is also profoundly dysregulated in the tumor microenvironment and antagonizes the development of tumor immunity. In this review, we discuss the biology of PS with respect to its role as a global immunosuppressive signal and how PS is exploited to drive diverse pathological processes such as infection and cancer. Finally, we outline the rationale that agents targeting PS could have significant value in cancer and infectious disease therapeutics.
Silicon nitride ceramics are used under conditions where high strength, hardness, and wear resistance are necessary. The increasing use of Si3N4 ceramics in different environments demands an ...understanding of the relationships between microstructure and corrosion behavior. This study gives an overview of the behavior of silicon nitride in acids, bases, and hydrothermal conditions. It not only summarizes the literature data but also attempts to explain the mechanisms and to give some guidelines for the use of the materials in different environments. The stability of the ceramics against corrosion in acids and bases up to the boiling point is mostly controlled by the stability of the grain boundary. The stability can be predicted using the glass network theory. Materials with grain boundaries exhibiting a strong network, i.e., a high amount of SiO2 in the grain boundary, are stable in acids, but less stable under hydrothermal conditions and in basic solutions. Therefore, tailoring the grain boundaries can change the corrosion stability by several orders of magnitude. At temperatures above 200°C–250°C, the dissolution of the Si3N4 grains becomes a decisive factor determining the stability.
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