New imaging technology reveals VPS13A protein's role in lipid transport between cellular organelles
Researchers have developed a technology to image phosphatidylethanolamine (PE) lipids in live mammalian cells using a metabolic labeling approach combined with click chemistry fluorescence. The method relies on an azido ethanolamine derivative that selectively labels PE without being converted into other lipid species, overcoming a key specificity challenge. The tool enabled the discovery that the protein VPS13A transports PE from the endoplasmic reticulum to mitochondria, with broad implications for understanding lipid trafficking and related diseases.
Scientists have developed a lipid imaging platform that allows real-time visualization of phosphatidylethanolamine (PE), a major membrane lipid, in living mammalian cells. By screening a library of ethanolamine derivatives, the team identified an azido-tagged compound that metabolically incorporates into PE while evading cellular methylation enzymes, ensuring it does not inadvertently label methylated PE or phosphatidylcholine (PC). Cyclooctyne-based fluorescent dyes were then applied to cells carrying the azido-PE probe, rendering the labeled lipids fluorescent through strain-promoted click chemistry. Using this approach, the researchers imaged PE across multiple organelles, tracked PE externalization during apoptosis—a known cell death signal—and demonstrated that VPS13A functions as a PE lipid transfer protein shuttling PE from the endoplasmic reticulum to mitochondria. VPS13A mutations are linked to a rare neurodegenerative disorder called chorea-acanthocytosis, making this mechanistic finding potentially relevant to disease. The technology addresses a longstanding gap in cell biology, as imaging specific lipid subtypes in live cells has historically been technically difficult. The authors anticipate the platform will be broadly useful for studying PE dysregulation in disease contexts.
What's missing
The study is a preprint posted on bioRxiv and has not yet undergone peer review, so findings should be interpreted with appropriate caution. The authors do not report whether VPS13A-mediated PE transfer was validated in disease-relevant cell models (e.g., chorea-acanthocytosis patient cells), leaving the clinical implications speculative.
What different sources said
- bioRxivCenter
A metabolic labelling-based lipid imaging technology establishes VPS13A as a phosphatidylethanolamine lipid transfer protein
Related
Gut Bacteria Enzyme Found to Break Down Heat-Processed Food Compounds, Producing Novel Biogenic Amines
Researchers have discovered that an enzyme in common gut bacteria can degrade N-epsilon-carboxymethyllysine (CML), a compound formed during thermal food processing, producing previously unknown biogenic amines. The enzyme, ornithine decarboxylase SpeC from enterobacteria, acts on CML and related modified lysine derivatives through a low-level 'underground' catalytic activity. This finding suggests a previously unrecognized communication axis between thermally processed dietary compounds and gut microbial physiology, with potential implications for host health.
Full-Length Gene Sequencing Reveals Two Distinct Bacterial Communities in Black-Legged Ticks Expanding Into Canada
Researchers used Oxford Nanopore full-length 16S rRNA gene sequencing to characterize the microbiome of Ixodes scapularis black-legged ticks collected in Nova Scotia, Canada, distinguishing between tick-adapted bacteria and environmentally acquired bacteria. The study comes as I. scapularis — the primary vector of Lyme disease — is rapidly expanding northward into Canada due to climate change. The findings suggest that environmentally derived bacteria in tick microbiomes are not mere contamination, which has implications for how tick microbiome data is collected and interpreted across surveillance studies.
Study Identifies Metabolic Link Between Cell Envelope Stress and Biofilm Formation in Bacteria
Researchers have discovered that the metabolite acetyl-CoA directly inhibits enzymes that degrade the bacterial signaling molecule c-di-GMP, connecting cell envelope biosynthesis stress to biofilm formation in Pseudomonas aeruginosa. The study found that sub-inhibitory concentrations of antibiotics targeting early peptidoglycan biosynthesis — but not other antibiotic classes — elevate c-di-GMP levels by reducing phosphodiesterase activity, with acetyl-CoA competing for the enzyme active site. Because the relevant enzyme domain is broadly conserved across bacterial species, this checkpoint mechanism may be widespread and could have implications for understanding antibiotic-induced biofilm responses.