Vera Skafar

The metabolic code of ferroptosis: nutritional regulators of cell death Ferroptosis is a distinctive form of regulated cell death driven by iron-dependent phospholipid peroxidation. Its initiation and suppression are finely tuned by metabolic pathways, transcription facto...

🔊Check out the August issue in @cp-trendsbiochem.bsky.social - and don't miss our contribution

We highlight recent advances in understanding how #metabolites and #nutrients shape susceptibility to #ferroptosis

www.cell.com/trends/bioch...

Riboflavin metabolism shapes FSP1-driven ferroptosis resistance Membrane protection against oxidative insults is achieved by the concerted action of glutathione peroxidase 4 (GPX4) and endogenous lipophilic antioxidants such as ubiquinone and vitamin E. Deficienci...

🚨Preprint alert 🚨

We identify riboflavin (vitamin B₂) as a key modulator of ferroptosis sensitivity via stabilizing FSP1 & recycling lipid-soluble antioxidants.

www.biorxiv.org/content/10.1....

pls check @olzmannlab.bsky.social

www.biorxiv.org/content/10.1...

#ferroptosis #FSP1 #antioxidants

Cell death: Dynamics and compartmentalization of NADH and FSP1 in ferroptosis A new study identifies the aldehyde dehydrogenase ALDH7A1 as a key regulator of ferroptosis. ALDH7A1 generates a pool of membrane-associated NADH, which is used by ferroptosis suppressor protein 1 to ...

Happy to see our highlight out discussing new findings related to NADH and FSP1 compartmentalization in ferroptosis. Lead by two terrific postdocs Amalia Megarioti and Kirandeep Deol! 🤩 👏
www.cell.com/current-biol...

Mitochondria complex III–generated superoxide is essential for IL-10 secretion in macrophages Mitochondrial ROS is necessary for the release of a critical anti-inflammatory cytokine.

Oxidants are also signaling molecules. Cool work 🤩

Mitochondria complex III–generated superoxide is essential for IL-10 secretion in macrophages | Science Advances www.science.org/doi/10.1126/...

Are groundbreaking science discoveries becoming harder to find? Researchers are arguing over whether ‘disruptive’ or ‘novel’ science is waning – and how to remedy the problem.

A feature in Nature examines the debate among researchers over whether ‘disruptive’ or ‘novel’ science is waning and how to remedy the problem. 🧪

Online now - the Review "The metabolic code of #ferroptosis: nutritional regulators of cell death" from @angelifriedmann.bsky.social @k-hadian.bsky.social and colleagues.

#LipidPeroxidation #Nutrients #Metabolites #Vitamins #Lipids

Read it here 👉 authors.elsevier.com/sd/article/S...

Congrats, Ivan! 🎉

eSylites: Synthetic Probes for Visualization and Topographic Mapping of Single Excitatory Synapses The spatiotemporal organization of the postsynaptic density (PSD) is a fundamental determinant of synaptic transmission, information processing, and storage in the brain. The major bottleneck that prevents the direct and precise representation of the nanometer-scaled organization of excitatory glutamatergic synapses is the size of antibodies, nanobodies, and the genetically encoded fluorescent tags. Here, we introduce small, high affinity synthetic probes for simplified, high contrast visualization of excitatory synapses without the limitations of larger biomolecules. In vitro binding quantification together with microscopy-based evaluation identified eSylites, a series of fluorescent bivalent peptides comprising a dye, linker, and sequence composition that show remarkable cellular target selectivity. Applied on primary neurons or brain slices at nanomolar concentrations, eSylites specifically report PSD-95, the key orchestrator of glutamate receptor nanodomains juxtaposed to the presynaptic glutamate release sites that mediate fast synaptic transmission. The eSylite design minimizes a spatial dye offset and thereby enables visualization of PSD-95 with improved localization precision and further time-resolved discrimination. In particular, we find that individual dendritic spines can contain separate nanodomains enriched for either PSD-95 or its closest homologues, PSD-93 or SAP102. Collectively, these data establish eSylites as a broadly applicable tool for simplified excitatory synapse visualization, as well as a high-end microscopy compatible probe for resolving the PSD organization with unprecedented resolution.

🚀 Excited to share our latest work in #JACS on eSylites!

—Synthetic, high-affinity #ChemicalBiology probes for #SuperResolution #Synapse visualization & precise mapping in neurons and brain slices—without the need for antibodies, tags, or transfection!

📢 Read more: pubs.acs.org/doi/10.1021/...

@veraskafar.bsky.social 🧉❤️

An interesting example of #redoxepigenetics in the opposite direction whereby Nupr promoter demethylation drives iron sequestration by lipocalin-2 (lcn2) to reduce iron driven redox dependent cell death

After we reach advanced age, around 80, the propensity to develop cancer is markedly reduced. A discovery reported at Nature today about aged stem cells and iron insufficiency may help explain this advantage

www.nature.com/articles/d41...

Temporary HMCES-DNA cross-link prevents permanent DNA damage HMCES, a recently discovered but ancient protein, covalently attaches to damaged single-stranded DNA and shields it from nucleases. Rua-Fernandez and colleagues now show that HMCES catalyzes its own recycling, permitting normal growth and non-mutagenic DNA repair.

Long time not posting about #redoxepigenetics - today the focus is on HMCES a protein that binds to abasic DNA sites caused for instance by guanine oxidation and removed by BER - by protecing those sites HMCES prevents irreparable DNA damage www.cell.com/cell-reports...

Hierarchical determinants of the oxidation-induced mutational landscape in human cells 8-oxoguanine (8-oxoG) is a common oxidative DNA lesion, which causes G>T substitutions that compose COSMIC single base substitution signature 18 (SBS18) in human cancers. Determinants of local and reg...

This article generated a lot of discussion at #SfRBM2024 and spurred vigorous brain storming sessions - how come 8-oxodG promotes mutations at the most hindered regions of the genome? this is contrary to established paradigm and a phenomenal #redoxepigenetics advance www.biorxiv.org/content/10.1...

We're glad you think so! We commissioned them from Davide Bonazzi :)

The illustrations in eLife are so good! 🥰

😍

@veraskafar.bsky.social u this week

Antibody mimicry of a substrate to block flu neuraminidases!

I'm interested in all aspects related to autoimmunity. Looking for fellows on Blue Sky!