Biology subjects

Meister, I.

Publications and source records attributed to Meister, I..

5 recordsLinked to original sources

bioRxiv2026

A transporter essential for apical secretory organelles homeostasis in Toxoplasma gondii

Apicomplexan parasites rely on the rhoptries and micronemes to coordinate egress, motility, and host cell invasion. In Toxoplasma gondii, mechanistic insights into the control of these organelles lipid composition remain sparse. Although nearly 60 T. gondii Major Facilitator Superfamily (MFS) are predicted, many remain functionally uncharacterized. The MFS protein HAP12 was previously annotated as an apicoplast protein contributing to invasion and organelle inheritance. Based on localization and phylogenetic analyses, we show that HAP12 (renamed TFP5), is predominantly associated with the Golgi, with additional signal in the ELC and apical compartments, without convincing evidence of a major apicoplast-associated pool. Furthermore, TFP5 clusters with a subgroup of MFS transporter facilitator proteins (TFPs) involved in the morphological integrity of secretory apical organelles. TFP5 depletion results in defective microneme secretion and pronounced alterations in rhoptry morphology and positioning. Structural analyses revealed that TFP5 is strongly similar to MFSD2-like lipid transporters, while lipidomic analyses showed substantial changes in parasite lipid composition following TFP5 depletion. Together, these findings support a model in which TFP5 regulates lipid homeostasis required for the function of apical secretory organelles, thereby critically contributing to parasite virulence.

microbiology↗

bioRxiv2026

Hexose-6-phosphate dehydrogenase deficiency disrupts hepatic fatty acid homeostasis and induces triglyceride accumulation

Hexose-6-phosphate dehydrogenase (H6PD) catalyzes the first two steps of an endoplasmic reticulum-specific pentose phosphate pathway, regenerating luminal NADPH levels in the process. Its function remains insufficiently well understood. Since expression of H6PD is notably high in the liver, we aimed to assess its role in hepatic metabolism. Considering the central role of the liver in lipid synthesis, breakdown and storage, we focused our efforts specifically on studying the effect of H6PD on hepatic lipid metabolism. An H6PD knockout mice strain was generated and characterized by liquid chromatography-high-resolution mass spectrometry (LC-HRMS)-based lipidomic and proteomic analyses of liver tissue. Lipidomics analysis revealed an overall increase in hepatic triglycerides and a specific increase in unsaturated long-chain triglycerides in H6PD knockout mice. Intracellular lipid accumulation was confirmed through Nile Red staining of liver sections. Functional enrichment analysis of proteomics data from the H6PD deficient mice identified a corresponding upregulation of multiple fatty acid metabolism-associated pathways. Additionally, an H6PD knockout AML12 cell line was generated through CRISPR/Cas9 and characterized by lipid staining and functional assays to assess metabolic outcomes. Loss of H6PD led to intracellular lipid accumulation, reduced mitochondrial {beta}-oxidation and increased sensitivity to lipotoxicity, even though fatty acids remained the cells' primary mitochondrial fuel. Ultimately, our results indicate that H6PD plays an as-of-yet undescribed role in hepatic lipid metabolism, implying a link between the availability of NADPH within the endoplasmic reticulum and fatty acid homeostasis.

systems biology↗

bioRxiv2026

Carbonyl stress primes the metastable aging brain for Alzheimer's disease

Alzheimers disease (AD) is defined by amyloid-{beta} (A{beta}) plaques and tau tangles, yet the inflammation that comes with it is only partly localized where those lesions accumulate. Using spatial transcriptomics on 16 human hippocampal sections containing adjacent cortex, we found that plaques concentrated in grey matter, especially cortex. In contrast, the strongest inflammatory response occupied white matter and increased with distance from A{beta}-positive spots. This inflammatory signature increased with Braak stage in an independent 31-subject hippocampal bulk proteomic cohort. The white-matter environment revealed a distinct chemistry, with lipidomics showing cortical white matter gaining cholesteryl esters, lysosomal storage lipids and peroxidation-prone polyunsaturated species while losing myelin lipids, alongside carbonyl, glycation and iron-handling signatures. In an external single-nucleus cohort, an oligodendrocyte lipid-droplet program tracked cognitive decline after adjustment for amyloid and tangles, and the same reactive-glia chemistry recurred above expression-matched nulls across seven neurodegenerative datasets. We propose that this lipid-rich glial environment is a metastable, primed state, and that A{beta} and tau act as catalysts that tip it toward a self-sustaining inflammatory reaction. HighlightsO_LIPlaques concentrate in grey matter, whereas inflammatory programs increase with distance and peak in glial/myelin-rich white matter. C_LIO_LIThe white-matter response strengthens with Braak stage and is characterized by carbonyl stress, lipid storage, and myelin loss. C_LIO_LIAn oligodendrocyte lipid-droplet program tracks cognitive decline after adjustment for A{beta} and tau. C_LIO_LIA lipid-droplet reactive-glial state recurs across neurodegenerative diseases with distinct triggers and vulnerable cells. C_LIO_LIA{beta} and pTau may tip a metastable tissue environment already primed by lipid and carbonyl stress. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=188 SRC="FIGDIR/small/740487v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@127708borg.highwire.dtl.DTLVardef@4dc7b4org.highwire.dtl.DTLVardef@72350corg.highwire.dtl.DTLVardef@1f8d016_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2025

Neurotoxicity of Propylene Glycol Butyl Ether: Multiomic Evidence from Human BrainSpheres

Exposure to solvents may contribute to the development of neurodevelopmental and neurodegenerative diseases. Glycol ethers consist in a widely used class of organic solvents leading to workers and consumers exposure via many different applications. Ethylene glycol ethers are gradually being replaced by propylene glycol ethers thought to be less toxic. However, their neurotoxicity is not systematically assessed prior to placing them on the market. Therefore, this study investigated the potential neurotoxicity of propylene glycol butyl ether (PGBE) for which no official occupational limit has been established. To this aim, new approach methodologies have been used. Human induced pluripotent stem cells-derived BrainSpheres model was exposed to PGBE and to its main metabolite, 2-butoxypropanoic acid (2BPA). An integrative multiomic approach (transcriptomics, proteomics, metabolomics and lipidomics) was adopted to assess molecular alterations, derive benchmark concentrations and define potential mechanisms of action. PGBE was neurotoxic at occupationally relevant exposure concentrations. This was shown for the first time in human cells. And, although PGBE was more cytotoxic than 2BPA, both compounds showed very similar neurotoxicity. PGBE and 2BPA strongly affected the cell cycle, induced oxidative stress and perturbed energy and lipid metabolism. They also targeted specific nervous system processes, such as axon guidance and synapse organization. Finally, 2BPA may trigger ferroptosis by increased iron uptake. Our results show an urgent need for public health authorities to carefully assess the risk glycol ethers pose to humans, to properly protect the workers as well as individuals in the general population unknowingly exposed from indoor air contaminations.

pharmacology and toxicology↗

bioRxiv2020

Untargeted LC-MS metabolomics for the analysis of micro-scaled extracellular metabolites from hepatocytes

Metabolome analysis in micro physiological models is a challenge due to the low volume of cell culture medium (CCM). Here, we report a LC-MS-based untargeted metabolomics protocol for the detection of hepatocyte extracellular metabolites from micro-scale samples of CCM. Using a single LC-MS method we have detected 57 metabolites of which 27 showed >2-fold shifts after 72-hours incubation. We demonstrate that micro-scale CCM samples can be used for modelling micro-physiological temporal dynamics in metabolite intensities. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=62 SRC="FIGDIR/small/312520v3_ufig1.gif" ALT="Figure 1"> View larger version (11K): org.highwire.dtl.DTLVardef@1b307e3org.highwire.dtl.DTLVardef@cada64org.highwire.dtl.DTLVardef@1c7fb70org.highwire.dtl.DTLVardef@4cb37f_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract C_FIG

bioengineering↗