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The observational difficulties and the complexity of earthquake physics have rendered seismic hazard assessment largely empirical. Despite increasingly high-quality geodetic, seismic and field observations, data-driven earthquake imaging yields stark differences and physics-based models explaining all observed dynamic complexities are elusive. Here we present data-assimilated three-dimensional dynamic rupture models of California's biggest earthquakes in more than 20 years: the moment magnitude (Mw) 6.4 Searles Valley and Mw 7.1 Ridgecrest sequence, which ruptured multiple segments of a non-vertical quasi-orthogonal conjugate fault system1. Our models use supercomputing to find the link between the two earthquakes. We explain strong-motion, teleseismic, field mapping, high-rate global positioning system and space geodetic datasets with earthquake physics. We find that regional structure, ambient long- and short-term stress, and dynamic and static fault system interactions driven by overpressurized fluids and low dynamic friction are conjointly crucial to understand the dynamics and delays of the sequence. We demonstrate that a joint physics-based and data-driven approach can be used to determine the mechanics of complex fault systems and earthquake sequences when reconciling dense earthquake recordings, three-dimensional regional structure and stress models. We foresee that physics-based interpretation of big observational datasets will have a transformative impact on future geohazard mitigation.
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PURPOSE: Navigator-based correction of rigid-body motion reconciling high precision with minimal acquisition, minimal calibration and simple, fast processing. METHODS: A short orbital navigator (2.3 ms) is inserted in a three-dimensional (3D) gradient echo sequence for human head imaging. Head rotation and translation are determined by linear regression based on a complex-valued model built either from three reference navigators or in a reference-less fashion, from the first actual navigator. Optionally, the model is expanded by global phase and field offset. Run-time scan correction on this basis establishes servo control that maintains validity of the linear picture by keeping its expansion point stable in the head frame of reference. The technique is assessed in a phantom and demonstrated by motion-corrected imaging in vivo. RESULTS: The proposed approach is found to establish stable motion control both with and without reference acquisition. In a phantom, it is shown to accurately detect motion mimicked by rotation of scan geometry as well as change in global B0 . It is demonstrated to converge to accurate motion estimates after perturbation well beyond the linear signal range. In vivo, servo navigation achieved motion detection with precision in the single-digit range of micrometers and millidegrees. Involuntary and intentional motion in the range of several millimeters were successfully corrected, achieving excellent image quality. CONCLUSION: The combination of linear regression and feedback control enables prospective motion correction for head imaging with high precision and accuracy, short navigator readouts, fast run-time computation, and minimal demand for reference data.
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Imageamento Tridimensional , Imageamento por Ressonância Magnética , Humanos , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Modelos Lineares , Retroalimentação , Estudos Prospectivos , Movimento (Física) , ArtefatosRESUMO
PURPOSE: To provide a navigator-based run-time motion and first-order field correction for three-dimensional human brain imaging with high precision, minimal calibration and acquisition, and fast processing. METHODS: A complex-valued linear perturbation model with feedback control is extended to estimate and correct for gradient shim fields using orbital navigators (2.3 ms). Two approaches for sensitizing the model to gradient fields are presented, one based on finite differences with three additional navigators, and another projection-based approximation requiring no additional navigators. A mechanism for noise decorrelation of the matrix and the data is proposed and evaluated to reduce unwanted parameter biases. RESULTS: The rigid motion and first-order field control achieves robust motion and gradient shim corrections improving image quality in a series of phantom and in vivo experiments with varying field conditions. In phantom scans, magnet drifts, forced gradient field perturbations and field distortions from shifts of a second bottle phantom are successfully corrected. Field estimates of the magnet drifts are in good agreement with concurrent field probe measurements. For in vivo scans, the proposed method mitigates field variations from torso motions while being robust to head motion. In vivo gradient field precisions were 30 nT / m $$ 30\;\mathrm{nT}/\mathrm{m} $$ along with single-digit micrometer and millidegree rigid precisions. CONCLUSION: The navigator-based method achieves accurate, high-precision run-time motion and field corrections with low sequence impact and calibration requirements.
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Hydrogen peroxide is a primary atmospheric oxidant significant in terminating gas-phase chemistry and sulfate formation in the condensed phase. Laboratory experiments have shown an unexpected oxidation acceleration by hydrogen peroxide in grain boundaries. While grain boundaries are frequent in natural snow and ice and are known to host impurities, it remains unclear how and to which extent hydrogen peroxide enters this reservoir. We present the first experimental evidence for the diffusive uptake of hydrogen peroxide into grain boundaries directly from the gas phase. We have machined a novel flow reactor system featuring a drilled ice flow tube that allows us to discern the effect of the ice grain boundary content on the uptake. Further, adsorption to the ice surface for temperatures from 235 to 258 K was quantified. Disentangling the contribution of these two uptake processes shows that the transfer of hydrogen peroxide from the atmosphere to snow at temperatures relevant to polar environments is considerably more pronounced than previously thought. Further, diffusive uptake to grain boundaries appears to be a novel mechanism for non-acidic trace gases to fill the highly reactive impurity reservoirs in snow's grain boundaries.
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Peróxido de Hidrogênio , Gelo , Neve/química , Gases , TemperaturaRESUMO
OBJECTIVE: As the world increasingly adopts renewable and sustainable energy systems, transitionary solutions include nuclear power, which currently provides 20% of the United States' electricity and is the largest single source of carbon-free electricity generation. Advanced reactors are a critical component of a carbon-free mixed energy portfolio that require careful design of first-of-a-kind control rooms. BACKGROUND: The application of Human Factors Engineering (HFE) is essential for scientific and iterative testing of novel human-system interface (HSI) concepts to ensure effective, efficient, and safe plant operations. Microworlds are simulators that use simplified physics models and control systems to distill nuclear power operations into essential functions. METHOD: HFE scientists used the Rancor Microworld Simulator to obtain preference and performance metrics for novel and traditional static HSI design styles. Participants comprised advanced reactor company employees and nuclear industry consultants. A mixture of quantitative and qualitative data was captured. RESULTS: There was a preference for the basic graphical style that included high contrast and traditional color scheme elements. No single HSI design outperformed the others, and the participants did not perform better using their preferred HSI style. CONCLUSION: This experiment is the first in a series of HFE testing for HSIs in advanced reactor control room development. Clear user preferences emerged for elements within static displays. The cutting-edge neumorphic style was the least preferred. Future directions include tests of dynamic displays. APPLICATION: HFE is used in evaluating and designing HSI devices that will improve the efficiency and safety of advanced nuclear power operations.
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The protease HtrA2 has a protective role inside mitochondria, but promotes apoptosis under stress. We previously identified the G399S HtrA2 mutation in Parkinson's disease (PD) patients and reported mitochondrial dysfunction in vitro. Mitochondrial dysfunction is a common feature of PD and related to neurodegeneration. Complete loss of HtrA2 has been shown to cause neurodegeneration in mice. However, the full impact of HtrA2 overexpression or the G399S mutation is still to be determined in vivo. Here, we report the first HtrA2 G399S transgenic mouse model. Our data suggest that the mutation has a dominant-negative effect. We also describe a toxic effect of wild-type (WT) HtrA2 overexpression. Only low overexpression of the G399S mutation allowed viable animals and we suggest that the mutant protein is likely unstable. This is accompanied by reduced mitochondrial respiratory capacity and sensitivity to apoptotic cell death. Mice overexpressing WT HtrA2 were viable, yet these animals have inhibited mitochondrial respiration and significant induction of apoptosis in the brain leading to motor dysfunction, highlighting the opposing roles of HtrA2. Our data further underscore the importance of HtrA2 as a key mediator of mitochondrial function and its fine regulatory role in cell fate. The location and abundance of HtrA2 is tightly controlled and, therefore, human mutations leading to gain- or loss of function could provide significant risk for PD-related neurodegeneration.
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Complexo de Proteínas da Cadeia de Transporte de Elétrons/genética , Mitocôndrias/genética , Proteínas Mitocondriais/genética , Mutação , Doença de Parkinson/genética , Serina Endopeptidases/genética , Animais , Apoptose , Encéfalo/metabolismo , Encéfalo/patologia , Respiração Celular , Modelos Animais de Doenças , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Feminino , Dosagem de Genes , Regulação da Expressão Gênica , Serina Peptidase 2 de Requerimento de Alta Temperatura A , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Proteínas Mitocondriais/metabolismo , Atividade Motora , Neurônios/metabolismo , Neurônios/patologia , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Fenótipo , Serina Endopeptidases/metabolismoRESUMO
Yersinia adhesin A (YadA) belongs to a class of bacterial adhesins that form trimeric structures. Their mature form contains a passenger domain and a C-terminal ß-domain that anchors the protein in the outer membrane (OM). Little is known about how precursors of such proteins cross the periplasm and assemble into the OM. In the present study we took advantage of the evolutionary conservation in the biogenesis of ß-barrel proteins between bacteria and mitochondria. We previously observed that upon expression in yeast cells, bacterial ß-barrel proteins including the transmembrane domain of YadA assemble into the mitochondrial OM. In the current study we found that when expressed in yeast cells both the monomeric and trimeric forms of full-length YadA were detected in mitochondria but only the trimeric species was fully integrated into the OM. The oligomeric form was exposed on the surface of the organelle in its native conformation and maintained its capacity to adhere to host cells. The co-expression of YadA with a mitochondria-targeted form of the bacterial periplasmic chaperone Skp, but not with SurA or SecB, resulted in enhanced levels of both forms of YadA. Taken together, these results indicate that the proper assembly of trimeric autotransporter can occur also in a system lacking the lipoproteins of the BAM machinery and is specifically enhanced by the chaperone Skp.
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Adesinas Bacterianas/metabolismo , Sequência Conservada , Evolução Molecular , Mitocôndrias/metabolismo , Multimerização Proteica , Adesinas Bacterianas/química , Células HeLa , Humanos , Membranas Mitocondriais/metabolismo , Proteínas Mitocondriais/metabolismo , Chaperonas Moleculares/metabolismo , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Transporte Proteico , Proteólise , Saccharomyces cerevisiae/metabolismoRESUMO
The vast majority of outer membrane (OM) proteins in Gram-negative bacteria belongs to the class of membrane-embedded ß-barrel proteins. Besides Gram-negative bacteria, the presence of ß-barrel proteins is restricted to the OM of the eukaryotic organelles mitochondria and chloroplasts that were derived from prokaryotic ancestors. The assembly of these proteins into the corresponding OM is in each case facilitated by a dedicated protein complex that contains a highly conserved central ß-barrel protein termed BamA/YaeT/Omp85 in Gram-negative bacteria and Tob55/Sam50 in mitochondria. However, little is known about the exact mechanism by which these complexes mediate the integration of ß-barrel precursors into the lipid bilayer. Interestingly, previous studies showed that during evolution, these complexes retained the ability to functionally assemble ß-barrel proteins from different origins. In this review we summarize the current knowledge on the biogenesis pathway of ß-barrel proteins in Gram-negative bacteria, mitochondria and chloroplasts and focus on the commonalities and divergences that evolved between the different ß-barrel assembly machineries.
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Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas de Cloroplastos/metabolismo , Proteínas Mitocondriais/metabolismo , Multimerização Proteica , Proteínas da Membrana Bacteriana Externa/química , Evolução Biológica , Proteínas de Cloroplastos/química , Cloroplastos/química , Cloroplastos/metabolismo , Bactérias Gram-Negativas/química , Bactérias Gram-Negativas/metabolismo , Mitocôndrias/química , Mitocôndrias/metabolismo , Membranas Mitocondriais/química , Membranas Mitocondriais/metabolismo , Proteínas Mitocondriais/química , Modelos Biológicos , Conformação ProteicaRESUMO
Membrane-embedded ß-barrel proteins are found in the outer membranes (OM) of Gram-negative bacteria, mitochondria and chloroplasts. In eukaryotic cells, precursors of these proteins are synthesized in the cytosol and have to be sorted to their corresponding organelle. Currently, the signal that ensures their specific targeting to either mitochondria or chloroplasts is ill-defined. To address this issue, we studied targeting of the chloroplast ß-barrel proteins Oep37 and Oep24. We found that both proteins can be integrated in vitro into isolated plant mitochondria. Furthermore, upon their expression in yeast cells Oep37 and Oep24 were exclusively located in the mitochondrial OM. Oep37 partially complemented the growth phenotype of yeast cells lacking Porin, the general metabolite transporter of this membrane. Similarly to mitochondrial ß-barrel proteins, Oep37 and Oep24 expressed in yeast cells were assembled into the mitochondrial OM in a pathway dependent on the TOM and TOB complexes. Taken together, this study demonstrates that the central mitochondrial components that mediate the import of yeast ß-barrel proteins can deal with precursors of chloroplast ß-barrel proteins. This implies that the mitochondrial import machinery does not recognize signals that are unique to mitochondrial ß-barrel proteins. Our results further suggest that dedicated targeting factors had to evolve in plant cells to prevent mis-sorting of chloroplast ß-barrel proteins to mitochondria.
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Arabidopsis/metabolismo , Proteínas de Transporte/metabolismo , Proteínas de Cloroplastos/metabolismo , Mitocôndrias/metabolismo , Pisum sativum/metabolismo , Sinais Direcionadores de Proteínas/fisiologia , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Arabidopsis/genética , Transporte Biológico/fisiologia , Proteínas de Transporte/genética , Proteínas de Cloroplastos/genética , Expressão Gênica , Teste de Complementação Genética , Canais Iônicos , Mitocôndrias/genética , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial , Pisum sativum/genética , Proteínas de Plantas , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genéticaRESUMO
The destructive 2023 moment magnitude (Mw) 7.8-7.7 earthquake doublet ruptured multiple segments of the East Anatolian Fault system in Turkey. We integrated multiscale seismic and space-geodetic observations with multifault kinematic inversions and dynamic rupture modeling to unravel the events' complex rupture history and stress-mediated fault interactions. Our analysis reveals three subshear slip episodes during the initial Mw 7.8 earthquake with a delayed rupture initiation to the southwest. The Mw 7.7 event occurred 9 hours later with a larger slip and supershear rupture on its western branch. Mechanically consistent dynamic models accounting for fault interactions can explain the unexpected rupture paths and require a heterogeneous background stress. Our results highlight the importance of combining near- and far-field observations with data-driven and physics-based models for seismic hazard assessment.
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From California to British Columbia, the Pacific Northwest coast bears an omnipresent earthquake and tsunami hazard from the Cascadia subduction zone. Multiple lines of evidence suggests that magnitude eight and greater megathrust earthquakes have occurred - the most recent being 321 years ago (i.e., 1700 A.D.). Outstanding questions for the next great megathrust event include where it will initiate, what conditions are favorable for rupture to span the convergent margin, and how much slip may be expected. We develop the first 3-D fully dynamic rupture simulations for the Cascadia subduction zone that are driven by fault stress, strength and friction to address these questions. The initial dynamic stress drop distribution in our simulations is constrained by geodetic coupling models, with segment locations taken from geologic analyses. We document the sensitivity of nucleation location and stress drop to the final seismic moment and coseismic subsidence amplitudes. We find that the final earthquake size strongly depends on the amount of slip deficit in the central Cascadia region, which is inferred to be creeping interseismically, for a given initiation location in southern or northern Cascadia. Several simulations are also presented here that can closely approximate recorded coastal subsidence from the 1700 A.D. event without invoking localized high-stress asperities along the down-dip locked region of the megathrust. These results can be used to inform earthquake and tsunami hazards for not only Cascadia, but other subduction zones that have limited seismic observations but a wealth of geodetic inference.
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We present a dynamic rupture model of the 2016 Mw 7.8 Kaikoura earthquake to unravel the event's riddles in a physics-based manner and provide insight on the mechanical viability of competing hypotheses proposed to explain them. Our model reproduces key characteristics of the event and constraints puzzling features inferred from high-quality observations including a large gap separating surface rupture traces, the possibility of significant slip on the subduction interface, the non-rupture of the Hope fault, and slow apparent rupture speed. We show that the observed rupture cascade is dynamically consistent with regional stress estimates and a crustal fault network geometry inferred from seismic and geodetic data. We propose that the complex fault system operates at low apparent friction thanks to the combined effects of overpressurized fluids, low dynamic friction and stress concentrations induced by deep fault creep.
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ß-Barrel proteins are found in the outer membrane (OM) of Gram-negative bacteria, chloroplasts and mitochondria. The assembly of these proteins into the corresponding OM is facilitated by a dedicated protein complex that contains a central conserved ß-barrel protein termed BamA in bacteria and Tob55/Sam50 in mitochondria. BamA and Tob55 consist of a membrane-integral C-terminal domain that forms a ß-barrel pore and a soluble N-terminal portion comprised of one (in Tob55) or five (in BamA) polypeptide transport-associated (POTRA) domains. Currently the functional significance of this difference and whether the homology between BamA and Tob55 can allow them to replace each other are unclear. To address these issues we constructed hybrid Tob55/BamA proteins with differently configured N-terminal POTRA domains. We observed that constructs harboring a heterologous C-terminal domain could not functionally replace the bacterial BamA or the mitochondrial Tob55 demonstrating species-specific requirements. Interestingly, the various hybrid proteins in combination with the bacterial chaperones Skp or SurA supported to a variable extent the assembly of bacterial ß-barrel proteins into the mitochondrial OM. Collectively, our findings suggest that the membrane assembly of various ß-barrel proteins depends to a different extent on POTRA domains and periplasmic chaperones.
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Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas da Membrana Bacteriana Externa/química , Proteínas da Membrana Bacteriana Externa/genética , Escherichia coli/química , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/genética , Evolução Molecular , Mitocôndrias/genética , Proteínas Mitocondriais/química , Proteínas Mitocondriais/genética , Domínios Proteicos , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genética , Homologia de Sequência , Especificidade da EspécieRESUMO
A cost effective and sustainable supply of biomass feedstocks is a critical component of a viable biorefinery industry that is capable of making a credible impact on petroleum displacement. Feedstock costs can amount to a very significant fraction of the cost of the final biorefinery product. Thus, the reduction of the costs of feedstock production, harvest, collection, transportation, storage, and preprocessing can have a direct and positive effect on the overall viability of a given biorefinery. In addition, the feedstock and technology choices that are made for maintaining a sustainable biomass supply will have important implications not only for the biorefinery industry, but also for society as a whole. This session focused on feedstock supply, logistics, processing and composition, all of which are important elements of the feedstock supply chain.
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Fenômenos Biomecânicos/métodos , Hordeum/fisiologia , Teste de Materiais/métodos , Triticum/fisiologia , Zea mays/fisiologia , Força Compressiva , Elasticidade , Análise de Alimentos/métodos , Resistência à TraçãoAssuntos
Biomassa , Água/química , Catálise , Etanol/química , Rutênio/química , Espectroscopia por Absorção de Raios XRESUMO
Beta-barrel proteins are found in the outer membrane of Gram-negative bacteria, mitochondria, and chloroplasts. The evolutionary conservation in the biogenesis of these proteins allows mitochondria to assemble bacterial ß-barrel proteins in their functional form. In this chapter, we describe exemplarily how the capacity of yeast mitochondria to process the trimeric autotransporter YadA can be used to study the role of bacterial periplasmic chaperones in this process.
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Adesinas Bacterianas/biossíntese , Mitocôndrias/metabolismo , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/genética , Adesinas Bacterianas/química , Adesinas Bacterianas/genética , Adesinas Bacterianas/metabolismo , Western Blotting , Eletroforese em Gel de Poliacrilamida , Ensaio de Imunoadsorção Enzimática , Interleucina-8/metabolismo , Estrutura Secundária de Proteína , Transformação GenéticaRESUMO
Pedestrian safety is a significant problem in the United States, with thousands being injured each year. Multiple risk factors exist, but one poorly understood factor is pedestrians' ability to attend to vehicles using auditory cues. Auditory information in the pedestrian setting is increasing in importance with the growing number of quieter hybrid and all-electric vehicles on America's roadways that do not emit sound cues pedestrians expect from an approaching vehicle. Our study explored developmental differences in pedestrians' detection and localization of approaching vehicles. Fifty children ages 6-9 years, and 35 adults participated. Participants' performance varied significantly by age, and with increasing speed and direction of the vehicle's approach. Results underscore the importance of understanding children's and adults' use of auditory cues for pedestrian safety and highlight the need for further research.
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Limiar Auditivo , Automóveis , Segurança , Localização de Som , Adulto , Fatores Etários , Análise de Variância , Criança , Desenvolvimento Infantil , Feminino , Humanos , Masculino , Movimento (Física) , Análise e Desempenho de TarefasRESUMO
Pedestrians must use a variety of cues when making safe decisions, many of which require processing of auditory information. We examined detection and localization of approaching vehicles using auditory cues. 50 adults ages 18-49 were presented with actual sounds of vehicles approaching at 5, 12, 25, and 35 mph. Three indices were of interest: the distance at which vehicles were detected, participants' decision regarding the direction from which vehicles were approaching, and their determination of the vehicles' arrival at their location. Participants more easily detected vehicles moving at higher speeds and vehicles approaching from the right. Determination of the direction of approach reached 90% accuracy or better when vehicles were traveling at, or greater than, 12 mph, and were more approaching from the right. Determination of vehicle arrival deteriorated significantly as speeds increased. Implications of the use of auditory cues in pedestrian settings, and future directions, are discussed.
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Acidentes de Trânsito/psicologia , Percepção Auditiva , Movimento (Física) , Veículos Automotores , Acidentes de Trânsito/prevenção & controle , Adolescente , Adulto , Análise de Variância , Sinais (Psicologia) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Segurança , Localização de Som , Percepção Espacial , Percepção do Tempo , Adulto JovemRESUMO
ß-barrel proteins are found in the outer membranes of eukaryotic organelles of endosymbiotic origin as well as in the outer membrane of Gram-negative bacteria. Precursors of mitochondrial ß-barrel proteins are synthesized in the cytosol and have to be targeted to the organelle. Currently, the signal that assures their specific targeting to mitochondria is poorly defined. To characterize the structural features needed for specific mitochondrial targeting and to test whether a full ß-barrel structure is required, we expressed in yeast cells the ß-barrel domain of the trimeric autotransporter Yersinia adhesin A (YadA). Trimeric autotransporters are found only in prokaryotes, where they are anchored to the outer membrane by a single 12-stranded ß-barrel structure to which each monomer is contributing four ß-strands. Importantly, we found that YadA is solely localized to the mitochondrial outer membrane, where it exists in a native trimeric conformation. These findings demonstrate that, rather than a linear sequence or a complete ß-barrel structure, four ß-strands are sufficient for the mitochondria to recognize and assemble a ß-barrel protein. Remarkably, the evolutionary origin of mitochondria from bacteria enables them to import and assemble even proteins belonging to a class that is absent in eukaryotes.