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Here, using a genome-wide CRISPR screen, Bitew et al. identify GRA38, a phosphatidic acid phosphatase, as a key factor in Toxoplasma gondii adaptation to lipid-rich conditions via keeping lipid balance, sustaining growth, ultimately ensuring survival.

Here, the authors compared measurements between 34 laboratories from 19 countries, to quantify by mass spectrometry four ceramides of clinical relevance in human blood plasma Standard Reference Materials. The main goals were to evaluate concordance obtained in a large inter-laboratory trial and to report absolute concentrations of four circulating lipids in a publicly available standard.

Understanding the mechanisms underlying the survival of drug tolerant persister cells following chemotherapy remains elusive. Here, multi-omics analysis and experimental approaches show that the germ-cell-specific H3K4 methyltransferase PRDM9 promotes metabolic rewiring in glioblastoma stem cells.

Human proteins SERINC3 and SERINC5 are HIV-1 restriction factors that reduce viral infectivity. Here, the authors show that SERINC3 has architecture resembling non-ATP dependent lipid transporters and induces loss of membrane asymmetry correlated with changes in envelope conformation and loss of infectivity.

Lipid droplets are subcellular fat storage structures that are affected by environmental temperature, though precisely how is unclear. Here, they show that high temperatures promote the fusion of small lipid droplets into giant ones in C. elegans and that dietary omega-3 fats enhance lipid droplet fusion.

The small transmembrane protein NINJ1 promotes plasma membrane rupture in lytic cell death associated with pyroptosis, necrosis and apoptosis.

Glutathione has pleiotropic functions in different organs. Here the authors specifically examine deletion of a glutathione synthetic enzyme in the liver of adult mice and show that lack of glutathione affects lipid abundance through repressing NRF2.

Here the authors show how metabolic alteration of acyl chain composition affects phosphoinositide-driven signaling to initiate and sustain CD8⁺ T cell effector function during cell differentiation.

The role of peroxisomes in skeletal muscle remains largely unexplored. Here, the authors show that peroxisomal dysfunction and disrupted crosstalk with mitochondria drive age-related muscle decline, underscoring the need to preserve peroxisomes for muscle health.

Channelrhodopsins (ChRs) are primary tools for precise optical control over living cells. Structures of a viral ChR, OLPVR1, in closed (1.1 Å) and open (1.3 Å) states reveal the key details of its molecular mechanism.

Cryo-electron microscopy structures of native type A GABA receptors from human brain reveal diverse subunit compositions, protein binding partners and binding sites for antiepileptic drugs.

The authors show that sphingolipids, a class of fat molecules, accumulate in skeletal muscle during aging. They demonstrate that reducing sphingolipids improves age-related fitness in mice by enhancing the myogenic response of muscle and present genetic evidence that these findings may also translate to humans.

Current treatment options for ovarian cancer are limited to surgery and chemotherapy, but most patients experience recurrent metastatic diseases. Here, the authors develop an antigen–adjuvant combination immunotherapy for ovarian cancer by coupling tumor antigen loaded liposomes with plant virus adjuvant as a vaccine platform to prevent cancer recurrence and metastatic diseases.

Using highly purified protein factors, we provide evidence that BRCA1–BARD1 physically interacts with EXO1, BLM and WRN and upregulates the activity of all three resection pathways.

The linker for activation of T cells (LAT) protein is involved in the activation of T cells. Here the authors discover micron scale LAT condensation events downstream of singly bound T-cell receptors during T cell activation and characterise how LAT condensation timing affects downstream T cell signalling.

Multi-omic time course experiments reveal intricate biology of salt stress response mechanisms of the historically and industrially relevant algae, Scenedesmus obliquus UTEX393.

In this work, authors take a multiomics and microfluidics-based approach to elucidate the mechanism of endothelial damage in critical illness associated with SARS-CoV-2.

In biological systems, cells are divided into compartments, typically with lipid layers. Here, the authors design a multipart vesicle system for sequential enzymatic reactions, where the product from one reaction traverses into the next, allowing multiple spatially separated reaction steps.

Rhodopsin genes have been identified in some large double-stranded DNA viruses, but the structure and functions of viral rhodopsins remain unknown. Here authors present crystal structure and characterization of an Organic Lake Phycodnavirus rhodopsin II (OLPVRII) which forms a pentamer and is a weak proton pump.

During starvation, muscle strength and endurance, are still critical for survival. Seven days of complete fasting did not reduce maximal strength in leg muscles, but maximal endurance capacity was decreased because carbohydrate oxidation was restrained.

Nebulized mRNA delivery has broad therapeutic potential but has proven challenging. Here, the authors report on a modified lipid nanoparticle with improved conditions to allow nebulization and demonstrate its application for delivering mRNA to the lungs.

Fusion with the cell membrane is the earliest event in viral infection. Paludan and colleagues show that 'unscheduled' membrane-fusion events elicit an innate immune response dependent on the adaptor STING.

Sandhoff disease (SD) is a lysosomal storage disorder caused by deficiency in the β subunit of the β-hexosaminidase enzyme. Here, the authors show via bone marrow-based microglial replacement in a SD mouse model that myeloid-derived β-hexosaminidase is necessary for maintaining neuronal health.

Inhibition of ELOVL6, a fatty acid elongation enzyme, selectively degrades mutant KRAS, disrupts its membrane localization and suppresses tumor growth, revealing a novel vulnerability in KRAS-driven cancers.

Sterane molecular fossils with side-chain methylations have not been reported in the bacterial domain. One such sterane, 24-isopropylcholestane, has been attributed to ancient sponges, potentially representing the earliest evidence for animals on Earth. This study demonstrates that symbiotic bacteria are capable of producing the 24-isopropyl sterol side-chain, suggesting that bacteria should not be dismissed as sources of these biomarkers in the rock record.

Mutations in the CHKB gene cause muscular dystrophy. Here, the authors show that in mouse models of the disease changes in lipid metabolism are associated with decreased PPAR signaling, and show PPAR agonists can rescue expression of injury markers in myocytes in vitro.

Lentil-shaped phospholipid vesicles are sensitive to shear stress, offering a new class of materials that can deliver drugs in response to rheological changes in the body.

The endoplasmic reticulum protein DFCP1 is found on omegasomes implicated in autophagosome biogenesis, but its function has remained unknown. Here, Nähse et al. show that DFCP1 is an ATPase that mediates selective autophagy by promoting constriction of large omegasomes.

The authors display the bottom-up design, assembly, and in-depth characterization of defined lipid-RNA structures in the core of lipid nanoparticles. The inverted structures are thermostable and provide better transfection over lamellar structures.

Small molecules targeting transient receptor potential (TRP) channels might be used to control pain. Here, Neuberger et al. report cryo-EM structures of human TRPV1 in the absence of added ligands or in the presence of the TRPV1-specific antagonist SB-366791, providing insights for the design of new promising analgesics.

Bio-mimetic motion has been hard to achieve due to a lack of biocompatible conditions. Here, the authors report the creation of a liposome-stabilised aqueous PEG/dextran Pickering-like emulsion system with motion induced by the Marangoni effect and characterised by negative chemotaxis.

Surface charge plays an important role in determining nanoparticle fate in vivo. Here the authors report on the development of a light triggered charge switching liposome and demonstrate light triggered liposome targeting, uptake and payload delivery in a zebrafish model.

X-ray crystallography and molecular dynamics simulations of the μ-opioid receptor reveal the conformational changes in the extracellular and intracellular domains of this G-protein-coupled receptor that are associated with its activation.

Functionalized InAs quantum dots emitting in the short-wavelength infrared spectral region enable functional biomedical imaging at unprecedentedly high spatial resolution, deep penetration and fast acquisition speeds.

Structures of the iron transporter ferroportin and the peptide hormone hepcidin suggest how iron homeostasis is tightly regulated.

Upon stimulation by agonist binding, the C-terminal regions of G-protein-coupled receptors (GPCRs) become phosphorylated by GPCR kinases, and phosphorylated GPCRs bind arrestin. Here the authors give structural insights into the phosphorylation induced conformational changes in GPCRs by performing NMR studies with the β2-adrenoceptor.

Long-circulating, transfection-competent LNP-mRNA systems are key for effective extrahepatic delivery. Here, authors show that LNPs with high bilayer lipid ratios yield high mRNA encapsulation, prolonged circulation, and enhanced transfection in extrahepatic tissues.

T cells can use TCR on microvilli to interact with peptide-MHC (pMHC) complexes on antigen presenting cells. Here the authors characterise how T cells use microvilli to interrogate reconstituted membranes for pMHC complexes and how this is regulated by a balance between glycoproteins/glycocalyces that reduce detection, and the small adhesion protein CD2, which enhances detection.

While HER2-targeted therapies such as trastuzumab can be effective in patients with breast cancer, resistance often develops. Here, the authors demonstrate that the histone reader ZYMND8 promotes glycerophospholipid metabolic reprogramming via c-Myc and cPLA2α to increase secretion of IL-27, mediating resistance to HER2-targeted antibodies in preclinical models of breast cancer.

Damage-associated molecular patterns (DAMPs) are released during necrotic cell death and contribute to driving inflammation. Rathinam and colleagues show that galectin-1 is a new DAMP that functions by inhibiting the receptor phosphatase CD45.

Here, Farley et al. perform untargeted lipidomics to assess how SARS-CoV-2 rewires host lipid metabolism. SARS-CoV-2 viral proteins specifically induce lipid droplet formation and dramatically change lipid metabolism to support infection; interfering with lipid metabolism using small molecule inhibitors decreases virus production.

Membrane fluidity is a crucial feature in understanding cellular physiology. This protocol describes a robust pipeline for measuring plasma membrane fluidity using confocal imaging and new environment-sensitive probes.

Radiotherapy can induce fibrosis in cancer patients, limiting its use in clinical settings. Here, the authors identify a differentially methylated enhancer of the lipid kinase DGKA in fibroblasts from breast cancer patients developing fibrosis after radiotherapy and they show that DGKA inhibition affects lipid homeostasis and reduces pro-fibrotic fibroblast activation.

Assembly of higher-order artificial vesicles can unlock new applications. Here, the authors use optical tweezers to construct user-defined 2D and 3D architectures of chemically distinct vesicles and demonstrate inter-vesicle communication and light-enabled compartment merging.

Stimulator of interferon genes (STING) is known to be involved in defence against DNA viruses, but its role in the control of RNA viruses remains poorly explored. Here the authors show that STING participates in an innate immune response to RNA virus infection in a cGAS-independent manner.

Lipid nanoparticles carrying plasmid DNA and an inflammation inhibitor enable longer transgene expression than mRNA nanoparticles.

Expression of Cas9 and gRNA from viral vectors in vivo may cause off-target activity. Here the authors present NanoMEDIC, which uses nanovesicles to transiently deliver editing machinery to hard-to-transfect cells.

MicroRNAs from head and neck cancer cells, shuttled to sensory neurons by extracellular vesicles, cause a shift to an adrenergic neuronal phenotype that promotes tumour progression.