Biology subjects

Barayeu, U.

Publications and source records attributed to Barayeu, U..

6 recordsLinked to original sources

bioRxiv2026

Glutaredoxins rapidly reduce glutathione hydroper- and polysulfides

Hydropersulfides have gained attention in cell biology as excellent nucleophiles and membrane-protective radical scavengers. They form perthiyl radicals, which terminate radical chain reactions through self-recombination, leading to the formation of polysulfides. It is currently unknown how polysulfides are subsequently reduced again in non-enzymatic or enzymatic metabolic pathways. Here we used stopped-flow kinetic measurements in combination with mass spectrometry to show that the model class I glutaredoxin from the malaria parasite Plasmodium falciparum (PfGrx) rapidly reduces the polysulfides glutathione trisulfide (GS3G) and glutathione tetrasulfide (GS4G), yielding the glutathionylated enzyme and the corresponding glutathione hydropersulfide GSSH and hydrotrisulfide GS3H. The second-order rate constants of these enzymatic reductions [≥]107 M-1s-1 are even slightly higher than for glutathione disulfide (GSSG). In contrast, PfGrx was inactive or only moderately active using cystine or cysteine trisulfide as oxi-dants. GSSH and GS3H are further reduced by PfGrx with second-order rate constants on the order of 106-107 M-1s-1, yielding the glutathionylated enzyme as well as hydrogen sulfide (H2S) and hydrogen disulfide (H2S2), respectively. Thus, glutaredoxins specifically recognize the glutathione moiety of glutathione (hydro)polysulfides and glutathione hydropersulfide. Due to the rapid reduction of glutathionylated glutaredoxins by reduced glutathione (GSH), glutathione (hydro)per/polysulfides are efficiently converted to GSSG and H2S or the corresponding hydrogen polysulfides. As a consequence, the steady-state concentration of glutathione (hydro)per/polysulfides should be tightly controlled in subcellular compartments containing active glutaredoxins and high GSH concentrations.

biochemistry↗

bioRxiv2026

Sulfide:quinone oxidoreductase drives mitochondrial supersulfide metabolism to regulate bioenergetics and longevity in eukaryotes

Sulfide:quinone oxidoreductase (SQR) is a critical enzyme that maintains sulfur metabolism by oxidizing sulfide to supersulfides, currently defined as sulfur metabolites with six valence electrons and no charge that are covalently catenated with other sulfur atoms and excludes disulfides. While SQR is known to contribute to mitochondrial electron transport, its physiological impact on systemic energy metabolism and longevity remains largely undefined. In this study, we investigated the role of SQR in mitochondrial bioenergetics and aging using SQR-deficient Schizosaccharomyces pombe ({Delta}hmt2) and a mitochondria-selective SQR-deficient (Sqrdl{Delta}N/{Delta}N) mice model. Functional analysis demonstrated that{Delta} hmt2 grew normally in glucose but not in glycerol, indicating impaired mitochondrial respiration. It showed reduced membrane potential, ATP, and lifespan. Consistent with the yeast findings, Sqrdl{Delta}N/{Delta}N mice exhibited accumulated levels of hydrogen sulfide and persulfides, and demonstrated impaired mitochondrial energy metabolism. Furthermore, supersulfide donor supplementation selectively conferred lifespan extension in wild-type yeast, but not in SQR-deficient strain, and similarly improved mitochondrial function exclusively in wild-type mouse embryonic fibroblasts, with no benefit observed in SQR-mutant counterparts. Together, our findings demonstrate that mitochondrial SQR plays an essential role in sulfur respiration, critically supporting mitochondrial function and organismal longevity across eukaryotes. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=175 SRC="FIGDIR/small/716515v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@d834forg.highwire.dtl.DTLVardef@127dc7dorg.highwire.dtl.DTLVardef@1fccb8eorg.highwire.dtl.DTLVardef@197e910_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIDeveloped an SQR-deficient S. pombe ({Delta}hmt2) model that exhibits sulfur metabolism, mitochondrial dysfunction, and shortened chronological lifespan C_LIO_LISulfide and supersulfide donors prolong yeast lifespan in a SQR-dependent manner C_LIO_LIMitochondrial SQR is essential for membrane potential formation and ATP production in yeast and mammals C_LI

biochemistry↗

bioRxiv2026

Representational Dynamics in the Hippocampus and Medial Prefrontal Cortex during Learning and Task Mastery

While the medial prefrontal cortex (mPFC) interacts with the hippocampus to support learning and consolidation, how its neural representations evolve remains unclear. We recorded population activity from CA1 and the mPFC as rats trained on radial maze tasks over weeks. Low-dimensional mPFC manifolds generated using UMAP or PCA embeddings initially tracked session progression, showing within-session drift. As animals gained task familiarity, this temporal tracking weakened; mPFC manifolds differentiated specific arms, mirroring hippocampal representations. Arm discriminability was selectively enhanced at locations requiring spatial choices, but weakened when such demands were absent. These findings demonstrate that systems consolidation does not uniformly promote cortical generalization. Instead, the mPFC may slowly refine representations in response to specific task demands to support tailored task schemas.

neuroscience↗

bioRxiv2024

Sulfite oxidase deficiency causes persulfidation loss and H2S release

Sulfite oxidase (SOX) deficiency is a rare inborn error of cysteine metabolism resulting in severe neurological damage. In patients, sulfite accumulates to toxic levels causing a raise in downstream products S-sulfocysteine (SSC), mediating excitotoxicity, and thiosulfate, a catabolic intermediate/product of H2S metabolism. Here, we report a full-body knock-out mouse model for SOX deficiency (SOXD) with a severely impaired phenotype. Amongst the urinary biomarkers, thiosulfate showed a 45-fold accumulation in SOXD mice representing the major excreted S-metabolite. Consistently, we found increased plasma H2S, which was derived from sulfite-induced release from persulfides as demonstrated in vitro and in vivo. Mass spectrometric analysis of total protein persulfidome identified a major loss of persulfidation in 20% of the proteome affecting enzymes in amino acids and fatty acid metabolism. Urinary amino acid profiles indicate metabolic rewiring suggesting partial reversal of the TCA cycle thus identifying a novel contribution of H2S metabolism and persulfidation in SOXD.

biochemistry↗

bioRxiv2023

Methane formation driven by light and heat prior to the origin of life

Methane is a potent greenhouse gas, which likely enabled the evolution of life by keeping the early Earth warm. Here, we demonstrate new routes towards abiotic methane formation under early-earth conditions from methylated sulfur and nitrogen compounds with prebiotic origin. These compounds are demethylated in Fenton reactions governed by ferrous iron and reactive oxygen species, produced by light and heat in aqueous environments. The reactions generate methyl radicals and ultimately release methane and ethane. Organic iron chelators enhance reaction rates and recycle ferric to ferrous complexes via ligand-to-metal charge transfer, establishing a light-driven iron redox cycle. This abiotic reaction facilitates methane and ethane formation across Earths humid realm, thereby shaping the chemical evolution of the atmosphere prior to the origin of life and beyond. One-Sentence SummaryUnder suboxic and anoxic conditions, iron and reactive oxygen species drive the global formation of methane in aqueous environments.

evolutionary biology↗

bioRxiv2023

DOPA residues endow collagen with radical scavenging capacity

Here we uncover collagen, the main structural protein of all connective tissues, as a redox-active material. We identify dihydroxyphenylalanine (DOPA) residues, post-translational oxidation products of tyrosine residues, to be common in collagen derived from different connective tissues. We observe that these DOPA residues endow collagen with substantial radical scavenging capacity. When reducing radicals, DOPA residues work as redox relay: they convert to the quinone and generate hydrogen peroxide. In this dual function, DOPA outcompetes its amino acid precursors and ascorbic acid. Our results establish DOPA residues as redox-active side chains of collagens, probably protecting connective tissues against radicals formed under mechanical stress and/or inflammation.

biophysics↗