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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 91 records · Page 5
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Implications of Local Cathode Structure in Solid-State Batteries

Solid-state batteries (SSBs) are promising candidates for energy storage systems—specifically for automotive applications—owing to their higher energy density and supreme safety. SSBs currently must improve area-specific cathode loadings as well as the electro-chemo-mechanical stability at high voltages. Composite cathodes in SSBs are comprised of active material, ion and electronic conductors, binders, and electronic conducting materials. In addition to experimental limitations with engineering thick cathode architectures, low utilization and chemomechanical degradation of the cathodes limit the performance of composite cathodes. Composite cathodes must optimize several parameters simultaneously to achieve high performances that include loading, electrochemically active surface area, mechanical resilience, and porosity. This chapter summarizes the current state-of-the-art applications with regard to composite cathodes for SSBs and provides insights into cathode architectures using geometric packing models. Tailoring ion and electron transport pathways within the electrode while mitigating operational stresses is crucial for achieving energy-dense cathode structres for SSBs.

Dixit, Marm↗
DOE OSTI2025

Iso-cost-performance of thermal energy storage

As thermal energy storage (TES) systems gain increasing recognition as next-generation energy storage solutions, evaluating their techno-economic performance is crucial. This perspective analyzes the cost-performance of latent heat-based TES systems and introduces the concept of iso-cost-performance—maintaining a constant cost per unit energy ($\$$/kWh) despite material degradation. Using an empirical degradation model, we show that after 1200 thermal cycles, the thermal conductivity and volumetric energy density of a paraffin-based phase change material (PCM) decreased by 36.0% and 26.1%, respectively, resulting in a 31.2% reduction in the figure of merit (FOM) and, consequently, the system cost-performance. However, by introducing thermally conductive additives to enhance effective thermal conductivity, the TES system can recover its initial FOM, achieving iso-cost-performance operation. This framework quantitatively demonstrates how degradation-mitigation strategies—such as improving thermal conductivity—can offset material degradations and maintain long-term cost-effectiveness. Beyond PCM-based TES, the proposed FOM-based approach provides a generalized pathway for cost-performance optimization across various TES technologies.

25 ENERGY STORAGE↗
DOE OSTI2020

Geochemical narrowing of cement fracture aperture during multiphase flow of supercritical CO2 and brine

For carbon capture and storage operations, wells are used as a necessary conduit for injecting CO2 at depth, but they can also act as leakage conduits if the cement seals are compromised. The specific objective of this research was to investigate the nature of self-healing of a fracture within cement under multiphase flow of CO2 and brine, and to compare this to a newly developed model. This was accomplished through a laboratory investigation, flowing reacting supercritical CO2 and brine through a cement fracture with multiphase flow. The influent end of the fracture was degraded as evidenced by the formation of cracks across the surface. At the effluent end of the fracture, the initial aperture of 137 µm was reduced to 50 µm. This reduction by 87 µm was similar to results from a recently developed model tested in this study, which predicted an aperture reduction of 80 µm. Our results demonstrated that the model accurately predicted the reactions which occurred in this multiphase flow system.

wellbore, cement, fracture, multiphase-flow, super↗
DOE OSTI2022

A polypeptide model for toxic aberrant proteins induced by aminoglycoside antibiotics

Aminoglycoside antibiotics interfere with the selection of cognate tRNAs during translation, resulting in the synthesis of aberrant proteins that are the ultimate cause of cell death. However, the toxic potential of aberrant proteins and how they avoid degradation by the cell’s protein quality control (QC) machinery are not understood. Here we report that levels of the heat shock (HS) transcription factor σ32 increased sharply following exposure of Escherichia coli to the aminoglycoside kanamycin (Kan), suggesting that at least some of the aberrant proteins synthesized in these cells were recognized as substrates by DnaK, a molecular chaperone that regulates the HS response, the major protein QC pathway in bacteria. To further investigate aberrant protein toxic potential and interaction with cell QC factors, we studied an acutely toxic 48-residue polypeptide (ARF48) that is encoded by an alternate reading frame in a plant cDNA. As occurred in cells exposed to Kan, σ32 levels were strongly elevated following ARF48 expression, suggesting that ARF48 was recognized as a substrate by DnaK. Paradoxically, an internal 10-residue region that was tightly bound by DnaK in vitro also was required for the ARF48 toxic effect. Despite the increased levels of σ32, levels of several HS proteins were unchanged following ARF48 expression, suggesting that the HS response had been aborted. Nucleoids were condensed and cell permeability increased rapidly following ARF48 expression, together suggesting that ARF48 disrupts DNA-membrane interactions that could be required for efficient gene expression. Our results are consistent with earlier studies showing that aberrant proteins induced by aminoglycoside antibiotics disrupt cell membrane integrity. Insights into the mechanism for this effect could be gained by further study of the ARF48 model system.

36 MATERIALS SCIENCE↗
DOE OSTI2025

Coupling of Lipid Peroxidation and Criegee Intermediate Mediated Autoxidation in the Heterogeneous Oxidation of Linoleic Acid Aerosols

Autoxidation is an established mechanism for the degradation of organic molecules, which is relevant in the atmosphere, combustion processes, the environment, and the rancidification of lipids (commonly known as lipid peroxidation). Autoxidation proceeds via radical chain reactions involving hydroxyl (•OH), peroxy (RO2•), and alkoxy radicals, which are also prominent oxidants in the atmosphere. Recent reports have provided evidence for an alternative autoxidation mechanism driven instead by Criegee intermediates (CIs), which are produced from the reaction of β-hydroxy peroxy radicals (β-OH-RO2•). This work evaluates the contributions of these two mechanisms in the •OH initiated heterogeneous oxidation of linoleic acid (LA) aerosols. Reaction kinetics and product distributions are monitored using a vacuum ultraviolet photoionization aerosol time-of-flight mass spectrometer. To explain the observed kinetics, a kinetic model is developed that incorporates both the conventional peroxidation and alternative CI-mediated autoxidation mechanisms. We observe that the CI-mediated autoxidation pathways enhance the heterogeneous autoxidation rate, while the peroxidation reactions, although present, contributes less to the overall oxidation rate. α-Acyloxyalkyl hydroperoxides (AAHPs) are identified as key indicators for bimolecular reactions of CI with LA, highlighting the role of LA as a CI scavenger. Moreover, the measured functionalized LA products with hydroxyl or carbonyl group(s), serve as markers for the peroxidation reactions. In summary, this work presents a quantitative framework to understand the coupled reaction network of •OH, RO2•, β-OH-RO2• radicals, and CI in driving heterogeneous autoxidation, which is crucial for understanding degradation mechanisms of organic molecules in the environment and atmosphere.

Criegee intermediate↗
DOE OSTI2026

Chemical and Structural Insights into Solid Electrolyte Interphase Evolution for Sodium Metal Electrodes

The solid electrolyte interphase (SEI) critically governs the reversibility of sodium metal batteries, through dynamically mediating ion transport and interfacial reactions. However, its kinetic evolution under operating conditions, and how it influences interfacial stability, remains poorly understood. Here, in this study, we reveal that the SEI undergoes coupled chemical and mechanical changes during sodium plating and stripping, leading to spatial and temporal heterogeneity that drives interfacial degradation. Synchrotron operando grazing-incidence wide-angle X-ray scattering and soft X-ray absorption spectroscopy capture the sequential formation and dissolution of inorganic SEI phases (NaF, NaH, NaOH, Na 2 PO 3 F), accompanied by depth-dependent alterations in organic SEI components. Mesoscale modeling connects this evolving SEI heterogeneity to localized current density fluctuations and stress accumulation at the Na interface, identifying pathways to electrically isolated sodium formation. These findings show that SEI instability fundamentally limits reversibility in sodium metal batteries, and that controlling SEI chemistry–mechanics coupling is essential to achieving its durability.

36 MATERIALS SCIENCE↗
DOE OSTI2022

Fabrication, thermal analysis, and heavy ion irradiation resistance of epoxy matrix nanocomposites loaded with silane-functionalized ceria nanoparticles

This paper describes a detailed understanding of how nanofillers function as radiation barriers within the polymer matrix, and how their effectiveness is impacted by factors such as composition, size, loading, surface chemistry, and dispersion. Here, we designed a comprehensive investigation of heavy ion irradiation resistance in epoxy matrix composites loaded with surface-modified ceria nanofillers, utilizing tandem computational and experimental methods to elucidate radiolytic damage processes and relate them to chemical and structural changes observed through thermal analysis, vibrational spectroscopy, and electron microscopy. A detailed mechanistic examination supported by FTIR spectroscopy data identified the bisphenol A moiety as a primary target for degradation reactions. Results of computational modeling by the Stopping Range of Ions in Matter (SRIM) Monte Carlo simulation were in good agreement with damage analysis from surface and cross-sectional SEM imaging. All metrics indicated that ceria nanofillers reduce the damage area in polymer nanocomposites, and that nanofiller loading and homogeneity of dispersion are key to effective damage prevention. The results of this study represent a significant pathway for engineered irradiation tolerance in a diverse array of polymer nanocomposite materials. Numerous areas of materials science can benefit from utilizing this facile and effective method to extend the reliability of polymer materials.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

High‐efficiency adsorption of various heavy metals by tea residue biochar loaded with nanoscale zero‐valent iron

Abstract Nanoscale zero‐valent iron (nZVI) loaded on tea residue biochar activated with phosphoric acid composites was synthesized. This adsorbent can efficiently adsorb multiple heavy metal ions such as Pb (II), Cr (III), Cu (II), and Ni (II) simultaneously. The adsorption process was found to follow the pseudo‐second‐order kinetic model. Equilibrium adsorption capacities reached 288.18, 162.34, 242.72, and 267.22 mg·g −1 for Pb(II), Cr(III), Cu(II), and Ni(II), respectively. The common interfering ions exhibited lower influence on its adsorption capacity. The adsorption mechanism includes reduction, ion exchange, surface complexation and precipitation. Furthermore, the waste adsorbent was converted into a catalyst in situ, which could catalyze the degradation of Congo red by establishing an electron transfer pathway. This research provides a new concept for the sustainable utilization of industrial tea residues and the harmless treatment of waste nZVI composite adsorbents.

Liu, Shuang↗
DOE OSTI2022

Flux balance analysis of the ammonia-oxidizing bacterium Nitrosomonas europaea ATCC19718 unravels specific metabolic activities while degrading toxic compounds

The ammonia-oxidizing bacterium Nitrosomonas europaea has been widely recognized as an important player in the nitrogen cycle as well as one of the most abundant members in microbial communities for the treatment of industrial or sewage wastewater. Its natural metabolic versatility and extraordinary ability to degrade environmental pollutants (e.g., aromatic hydrocarbons such as benzene and toluene) enable it to thrive under various harsh environmental conditions. Constraint-based metabolic models constructed from genome sequences enable quantitative insight into the central and specialized metabolism within a target organism. These genome-scale models have been utilized to understand, optimize, and design new strategies for improved bioprocesses. Reduced modeling approaches have been used to elucidate Nitrosomonas europaea metabolism at a pathway level. However, genome-scale knowledge about the simultaneous oxidation of ammonia and pollutant metabolism of N . europaea remains limited. Here, we describe the reconstruction, manual curation, and validation of the genome-scale metabolic model for N . europaea , i GC535. This reconstruction is the most accurate metabolic model for a nitrifying organism to date, reaching an average prediction accuracy of over 90% under several growth conditions. The manually curated model can predict phenotypes under chemolithotrophic and chemolithoorganotrophic conditions while oxidating methane and wastewater pollutants. Calculated flux distributions under different trophic conditions show that several key pathways are affected by the type of carbon source available, including central carbon metabolism and energy production.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Impact of Porcine Arterivirus, Influenza B, and Their Coinfection on Antiviral Response in the Porcine Lung

Interferon (IFN) cytokines induce an autonomous antiviral state in cells of the infected site to restrict virus spreading and critically regulate overall antiviral response. The antiviral state leads to host protection through expression of hundreds of IFN-stimulated genes that restrict viral infection through multiple mechanisms, for example, directly in viral genome degradation and indirectly through cellular metabolic inhibition. Young pigs were split into four treatment groups: control, porcine reproductive and respiratory syndrome virus (PRRSV, also known as porcine arterivirus) infected, influenza B virus (IBV) infected, and IBV/PRRSV coinfection. Lung tissue was collected at 3, 5, and 7 days post infection (dpi) for control, PRRSV and IBV/PRRSV coinfection, and at 3 and 5 dpi for IBV. Transcriptomic analysis, using usegalaxy.org tools, was performed against the S.scrofa 11.1 reference genome. Differentially expressed gene (DEG) analysis was carried out using DeSeq2 based on the model treatment + dpi + treatment:dpi + E. Downstream analysis examined the interaction of DEG at each dpi for over-enriched gene ontology (G.O.) terms and pathways. Comparisons of the infected groups vs. the controls yielded a total of (n = 1412) DEGs for the PRRSV group and (n = 1578) for the IBV/PRRSV group across all timepoints. The IBV group had (n = 64) total DEGs across 3 and 5 dpi. Expression data were considered statistically significant based on false discovery rate (FDR) ⫹ 0.1. Venn diagram comparisons of the DEGs across dpi showed that groups shared only 16 DEGs at 3 dpi, no DEGs were shared at 5 dpi, and for 7 dpi, only the PRRSV and IBV/PRRSV groups were compared and shared a total of 43 DEGs. Across the comparisons, differential expression was observed in antiviral genes such as IRF1, MX1, and OAS2. The IBV and IBV/PRRSV groups showed higher expression of antiviral genes at earlier dpi than the PRRSV group. Additionally, downregulated genes from the comparisons clustered around Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways effecting lung development and cellular integrity. Early expression of host IFN and antiviral genes may lead to viral RNA degradation, and assembly and transcription inhibition in the IBV infections. In comparison, expression of antiviral genes in the PRRSV group decreased across time. The decrease may explain why PRRSV infections persist, while IBV clears. Moreover, all infected groups showed prolonged upregulation in neutrophil degranulation pathway activity, possibly exacerbating symptomatic lung lesion pathology seen in these respiratory infections.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Gas-mediated defect engineering in earth-abundant Mn-rich layered oxides for non-aqueous sodium-based batteries

Gases are often by-products of battery materials during cell formation and degradation, affecting the cycle life and safety of rechargeable batteries. However, understanding gas-mediated (electro)-chemical reactions and nanoscale structural transformations during the synthesis of battery electrode materials remains challenging because of the lack of suitable characterization routes and the complexity of the interplay between thermodynamics and kinetics. Here, in this study, we use operando synchrotron X-ray diffraction, in situ transmission X-ray microscopy and multiscale modelling to elucidate the reaction pathways and microstructural defect development of earth-abundant Mn-rich layered oxides as positive electrode materials for sodium-based batteries. In particular, we demonstrate the dominant role of CO 2 over O 2 and H 2 O (g) in modulating the competition between entropy and enthalpy during solid-state synthesis. Using Ni 0.25 Mn 0.75 CO 3 as a model precursor, we reveal that CO 2 generation favours the formation of entropy-driven metastable intermediates, suppresses closed pore/nanovoids formation and decreases chemical heterogeneity and residual lattice strain of Mn-rich layered oxides during the synthesis. This result motivates a fast-sintering strategy to promote CO 2 release, which ultimately leads to improved chemo-mechanical and electrochemical stability of the Mn-rich positive electrodes when tested in non-aqueous Na metal coin cells.

36 MATERIALS SCIENCE↗
DOE OSTI2021

Fusion and fission events regulate endosome maturation and viral escape

Endosomes are intracellular vesicles that mediate the communication of the cell with its extracellular environment. They are an essential part of the cell’s machinery regulating intracellular trafficking via the endocytic pathway. Many viruses, which in order to replicate require a host cell, attach themselves to the cellular membrane; an event which usually initiates uptake of a viral particle through the endocytic pathway. In this way viruses hijack endosomes for their journey towards intracellular sites of replication and avoid degradation without host detection by escaping the endosomal compartment. Recent experimental techniques have defined the role of endosomal maturation in the ability of enveloped viruses to release their genetic material into the cytoplasm. Endosome maturation depends on a family of small hydrolase enzymes (or GTPases) called Rab proteins, arranged on the cytoplasmic surface of its membrane. Here, we model endosomes as intracellular compartments described by two variables (its levels of active Rab5 and Rab7 proteins) and which can undergo coagulation (or fusion) and fragmentation (or fission). The key element in our approach is the “per-cell endosomal distribution” and its dynamical (Boltzmann) equation. The Boltzmann equation allows us to derive the dynamics of the total number of endosomes in a cell, as well as the mean and the standard deviation of its active Rab5 and Rab7 levels. We compare our mathematical results with experiments of Dengue viral escape from endosomes. The relationship between endosomal active Rab levels and pH suggests a mechanism that can account for the observed variability in viral escape times, which in turn regulate the viability of a viral intracellular infection.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Stabilizing High–Nickel Cathodes with High–Voltage Electrolytes

Electrolytes connect the two electrodes in a lithium battery by providing Li + transport channels between them. Advanced electrolytes are being explored with high-nickel cathodes and the lithium-metal anode to meet the high energy density and cycle life goals, but the origin of the performance differences with different electrolytes is not fully understood. Here, the mechanisms involved in protecting the high-capacity, cobalt-free cathode LiNiO 2 with a model high-voltage electrolyte (HVE) are delineated. The kinetic barrier posed by a thick surface degradation layer with poor Li + -ion transport is found to be the major contributor to the fast capacity fade of LiNiO 2 with the conventional carbonate electrolyte. In contrast, HVE reduces the side reactions between the electrolyte and the electrodes, leading to a thinner nano-interphase layer comprised of more beneficial species. Crucially, the HVE leads to a different surface reorganization pathway involving the formation of a thinner nanoscale LiNi 2 O 4 spinel phase on the LiNiO 2 surface. Finally, with a high 3D Li + -ion and electronic conductivity, the spinel LiNi 2 O 4 reorganization nanolayer preserves fast Li + transport across the cathode–electrolyte interface, reduces reaction heterogeneity in the electrode and alleviates intergranular cracking within secondary particles, resulting in superior long-term cycle life.

25 ENERGY STORAGE↗
DOE OSTI2023

Advective gas flow in bentonite: Development and comparison of enhanced multi-phase numerical approaches

Understanding the impact of repository gas, generated from degradation of waste and its interaction with the host rock, is essential when assessing the performance and safety function of long-term disposal systems for radioactive waste. Numerical models based on conventional multi-phase flow theory have historically been applied to predict the outcome and impact of gas flow on different repository components. However, they remain unable to describe the full complexity of the physical processes observed in water-saturated experiments (e.g., creation of dilatant pathways) and thus, the development of novel representations for their description is required when assessing fully saturated clay-based systems. This was the primary focus of Task A within the international cooperative project DECOVALEX-2019 (D-2019) and refinement of these approaches is the primary focus of this study (Task B in the current phase of DECOVALEX-2023). This paper summarises development of enhanced numerical representations of key processes and compares the performance of each model against high-quality laboratory test data. Experimental data reveals that gas percolation in water-saturated compacted bentonite is characterised by four key features: (i) a quiescence phase, followed by (ii) the gas breakthrough, which leads to a (iii) peak value, which is then followed by (iv) a negative decay. Three models based on the multiphase flow theory have been developed. These models can provide good initial values and reasonable responses for gas breakthrough (although some of them still predict a too-smooth response). Peak gas pressure values are in general reasonably well captured, although maximum radial stress differences are observed at 48 mm from the base of the sample. Here, numerical peak values of 12.8 MPa are predicted, whereas experimental values are about 11 MPa. These models are also capable of providing a reasonable representation of the negative pressure decay following peak pressure. However, other key specific features (such as the timing of gas breakthrough) still require a better representation. The model simulations and their comparison with experimental data show that these models need to be further improved with respect to model parameter calibration, the numerical representation of spatial heterogeneities in material properties and flow localisation, and the upscaling of the related physical processes and parameters. To further understand gas flow localisation, a new conceptual model has been developed, which shows that discrete channels can possibly be induced through the instability of gas-bentonite interface during gas injection, thus providing a new perspective for modeling gas percolation in low-permeability deformable media.

58 GEOSCIENCES↗
DOE OSTI2025

NUB1 traps unfolded FAT10 for ubiquitin-independent degradation by the 26S proteasome

The ubiquitin-like modifier FAT10 targets hundreds of proteins in the mammalian immune system to the 26S proteasome for degradation. This degradation pathway requires the cofactor NUB1, yet the underlying mechanisms remain unknown. Here, we reconstituted a minimal in vitro system with human components and revealed that NUB1 uses the intrinsic instability of FAT10 to trap its N-terminal ubiquitin-like domain in an unfolded state and deliver it to the 26S proteasome for engagement, allowing the degradation of FAT10-ylated substrates in a ubiquitin-independent and p97-independent manner. Using hydrogen–deuterium exchange, structural modeling and site-directed mutagenesis, we identified the formation of an intricate complex with FAT10 that activates NUB1 for docking to the 26S proteasome, and our cryo-EM studies visualized the highly dynamic NUB1 complex bound to the proteasomal Rpn1 subunit during FAT10 delivery and the early stages of ATP-dependent degradation. These findings identified a previously unknown mode of cofactor-mediated, ubiquitin-independent substrate delivery to the 26S proteasome that relies on trapping partially unfolded states for engagement by the proteasomal ATPase motor.

Arkinson, Connor↗
DOE OSTI2023

Light-independent phytoplankton degradation and detoxification of methylmercury in water

Phytoplankton serves as a key entry point for the trophic transfer and bioaccumulation of the neurotoxin methylmercury (MeHg) in aquatic food webs. However, it is unclear whether and how phytoplankton itself may degrade and metabolize MeHg in the dark. Here, using several strains of the freshwater alga Chlorella vulgaris, the marine diatom Chaetoceros gracilis and two cyanobacteria (or blue-green algae), we report a light-independent pathway of MeHg degradation in water by phytoplankton, rather than its associated bacteria. About 36–85% of MeHg could be degraded intracellularly to inorganic Hg(II) and/or Hg(0) via dark reactions. Furthermore, endogenic reactive oxygen species, particularly singlet oxygen, were identified as the main driver of MeHg demethylation. Given the increasing incidence of algal blooms in lakes and marine systems globally, these findings underscore the potential roles of phytoplankton demethylation and detoxification of MeHg in aquatic ecosystems and call for improved modelling and assessment of MeHg bioaccumulation and environmental risks.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Light Water Reactor Sustainability Program Materials Research Pathway Technical Program Plan

The Materials Research (MR) Pathway within the Light Water Reactor Sustainability (LWRS) Program is charged with performing the research and development (R&D) to develop the scientific basis for understanding and predicting long-term environmental degradation behavior of materials in nuclear reactors. Furthermore, it is essential to use the mechanistic understanding of degradation phenomena in materials to develop mitigation, repair, and new material alternatives for existing components. The work will provide data and methods to assess performance of systems, structures, and components (SSCs) essential to safe and sustained reactor operations. The R&D products developed from the LWRS Program will be used by utilities, industry groups, and regulators to inform operational and regulatory requirements for materials in reactor SSCs subjected to long-term operation conditions, providing key input to both regulators and industry. The intent of this research is to help in reducing the operating costs, which may be in the form of offset maintenance costs due to better predictive models for component lifetimes, improved analysis of materials through nondestructive evaluation, reduced costs for repairs, or extended performance of plants through the selection of improved replacement materials. To best achieve this, industry experience and guidance are important as is their role in coordinated or collaborative research projects. The objectives of this report are to describe the motivation and organization of the MR Pathway within the LWRS Program, provide details on the individual research tasks within the MR Pathway, describe the outcomes and deliverables of the MR Pathway, including recent technical highlights and progress, and list the requirements for performing the research.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗
DOE OSTI2022

Fine-tuning of mTOR signaling by the UBE4B-KLHL22 E3 ubiquitin ligase cascade in brain development

ABSTRACT Spatiotemporal regulation of the mechanistic target of rapamycin (mTOR) pathway is pivotal for establishment of brain architecture. Dysregulation of mTOR signaling is associated with a variety of neurodevelopmental disorders. Here, we demonstrate that the UBE4B-KLHL22 E3 ubiquitin ligase cascade regulates mTOR activity in neurodevelopment. In a mouse model with UBE4B conditionally deleted in the nervous system, animals display severe growth defects, spontaneous seizures and premature death. Loss of UBE4B in the brains of mutant mice results in depletion of neural precursor cells and impairment of neurogenesis. Mechanistically, UBE4B polyubiquitylates and degrades KLHL22, an E3 ligase previously shown to degrade the GATOR1 component DEPDC5. Deletion of UBE4B causes upregulation of KLHL22 and hyperactivation of mTOR, leading to defective proliferation and differentiation of neural precursor cells. Suppression of KLHL22 expression reverses the elevated activity of mTOR caused by acute local deletion of UBE4B. Prenatal treatment with the mTOR inhibitor rapamycin rescues neurogenesis defects in Ube4b mutant mice. Taken together, these findings demonstrate that UBE4B and KLHL22 are essential for maintenance and differentiation of the precursor pool through fine-tuning of mTOR activity.

Kong, Xiangxing↗