Biology subjects

Batushansky, A.

Publications and source records attributed to Batushansky, A..

8 recordsLinked to original sources

bioRxiv2026

HDAC6 and SSAT2 orchestrate acetyllysine metabolism and protein homeostasis

Lysine acetylation is a prevalent and dynamic posttranslational modification, yet the metabolic fate and physiological role of free N {varepsilon}-acetyl-L-lysine (AcK) remain unclear. Here, we identify opposing enzyme-catalyzed reactions linking lysine/AcK homeostasis to protein stability. We show that the first catalytic domain of HDAC6 stereospecifically deacetylates free AcK, establishing HDAC6 as an N {varepsilon}-acyl-lysine deacylase. AcK functions both as a recyclable lysine reservoir and as a signaling metabolite that elevates -tubulin acetylation and suppresses cell migration. Conversely, SSAT2 acetylates free lysine in cells and undergoes substrate-dependent C-terminal autoacetylation. We demonstrate that C-terminal lysine acetylation constitutes a reversible proteasomal degradation signal that promotes SSAT2 degradation and may extend to additional proteins bearing a terminal lysine. Stabilization of SSAT2 by HDAC6-dependent deacetylation, together with intricate regulation affected by substrate availability, reveals a novel mechanism that couples amino acid recycling to cytoskeletal dynamics and proteostasis.

biochemistry↗

bioRxiv2026

The mitochondrial chaperone HSPD1 folds MTHFD2 independently of its co-chaperone HSPE1

Acquiring new cellular states entails metabolic reprogramming driven by changes in the expression of cytosolic and mitochondrial metabolic enzymes. Most mitochondrial proteins are synthesized in the cytosol and imported into the mitochondria in a linear form, after which they are folded by a network of mitochondrial chaperones and co-chaperones. Which mitochondrial protein is dependent upon which chaperone for its folding is largely unknown. HSPD1/HSPE1 (HSP60/HSP10) are evolutionarily conserved mammalian homologues of the bacterial proteins GroEL/GroES, forming a chamber-and-lid chaperonin to facilitate the folding of client proteins. We used gene knockdown and SILAC-based proteomics to identify HSPD1 client proteins. We found that HSPD1 supports the expression of Methylenetetrahydrofolate Dehydrogenase 2 (MTHFD2), a key essential protein in the mitochondrial one-carbon (1C) pathway, in cells and tumors, and directly folds MTHFD2, independently of its co-chaperone HSPE1. HSPD1 interacts with MTHFD2 in mitochondria, and MTHFD2 is degraded by LONP1 in HSPD1 knockdown cells. Consequently, we observed reduced nucleotide and S-adenosylmethionine (SAM) levels in HSPD1 knockdown and found minimal overlap in the transcriptional and metabolic cellular responses to HSPD1 vs. HSPE1 depletion. In C. elegans, knockout of HSP60 triggers the mitochondrial stress response in the gut, while HSP10 knockout triggers the mitochondrial stress response in muscle tissue. Our data support that HSPD1 is an MTHFD2 chaperone and that, in addition to working together, HSPD1 and HSPE1 have distinct biological functions.

cell biology↗

bioRxiv2025

Damselflies Overcome Color Saturation Barriers of Photonic Glasses via Structural Dispersion and Pigment Loading

Biologys strategies for manipulating light offer rich inspiration for the design of sustainable replacements to conventional pigments in paints, coatings, and displays. For these applications, where angle-independent color is required, photonic glasses, composed of random arrangements of dielectric spheres, offer a promising solution. However, their intrinsic disorder, particularly from particle polydispersity, fundamentally limits their color saturation and practical utility. In contrast, insects like damselflies and dragonflies exhibit surprisingly vivid, non-iridescent structural colors, despite relying on disordered photonic structures. Here, we show how damselflies combine compositional and structural dispersion to overcome color saturation limits of photonic glasses. Firstly, doping transparent particles with yellow pigments dramatically enhances blue-green structural resonances by the coupled effects of narrowband absorption and refractive index (material) dispersion. Secondly, the refractive index of the nanospheres varies with their size and crystallinity. This gives rise to a structural dispersion which maintains consistent optical path lengths in polydisperse assemblies, preserving high color purity. Finally, we show how damselflies tune their structural colors during maturation by precisely modulating the size of the nanospheres. Remarkably, the tuning of particle size, refractive index and pigment loading, arises naturally during the development of the pigment cells - where the pteridine nanospheres undergo a process of densification, crystallization and metabolic maturation.

animal behavior and cognition↗

bioRxiv2024

Title: Diurnal rhythms in durum wheat triggered by Rhopalosiphum padi (bird cherry-oat 2 aphid)

Wheat is a staple crop and one of the most widely consumed grains globally. Wheat yields can experience significant losses due to the damaging effects of herbivore infestation. However, little is known about the effect aphids have on the natural diurnal rhythms in plants. Our time-series transcriptomics and metabolomics study reveal intriguing molecular changes occurring in plant diurnal rhythmicity upon aphid infestation. Under control conditions, 15,366 out of the 66,559 genes in the tetraploid wheat cultivar Svevo, representing approximately 25% of the transcriptome, exhibited diurnal rhythmicity. Upon aphid infestation, 5,682 genes lost their rhythmicity, while additional 5,203 genes began to exhibit diurnal rhythmicity. The aphid-induced rhythmic genes were enriched in GO terms associated with plant defense, such as protein phosphorylation and cellular response to ABA and were enriched with motifs of the WRKY transcription factor families. Conversely, the genes that lost rhythmicity due to aphid infestation were enriched with motifs of the TCP and ERF transcription factor families. While the core circadian clock genes maintain their rhythmicity during infestation, we observed that approximately 60% of rhythmic genes experience disruptions in their rhythms during aphid infestation. These changes can influence both the plants growth and development processes as well as defense responses. Furthermore, analysis of rhythmic metabolite composition revealed that several monoterpenoids gained rhythmic activity under infestation, while saccharides retained their rhythmic patterns. Our findings highlight the ability of insect infestation to disrupt the natural diurnal cycles in plants, expanding our knowledge of the complex interactions between plants and insects.

plant biology↗

bioRxiv2023

Loss of cardiac PFKFB2 drives Metabolic, Functional, and Electrophysiological Remodeling in the Heart

BackgroundPhosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2) is a critical glycolytic regulator responsible for upregulation of glycolysis in response to insulin and adrenergic signaling. PFKFB2, the cardiac isoform of PFK-2, is degraded in the heart in the absence of insulin signaling, contributing to diabetes-induced cardiac metabolic inflexibility. However, previous studies have not examined how the loss of PFKFB2 affects global cardiac metabolism and function. MethodsTo address this, we have generated a mouse model with a cardiomyocyte-specific knockout of PFKFB2 (cKO). Using 9-month-old cKO and control (CON) mice, we characterized impacts of PFKFB2 on cardiac metabolism, function, and electrophysiology. ResultscKO mice have a shortened lifespan of 9 months. Metabolically, cKO mice are characterized by increased glycolytic enzyme abundance and pyruvate dehydrogenase (PDH) activity, as well as decreased mitochondrial abundance and beta oxidation, suggesting a shift toward glucose metabolism. This was supported by a decrease in the ratio of palmitoyl carnitine to pyruvate-dependent mitochondrial respiration in cKO relative to CON animals. Metabolomic, proteomic, and western blot data support the activation of ancillary glucose metabolism, including pentose phosphate and hexosamine biosynthesis pathways. Physiologically, cKO animals exhibited impaired systolic function and left ventricular (LV) dilation, represented by reduced fractional shortening and increased LV internal diameter, respectively. This was accompanied by electrophysiological alterations including increased QT interval and other metrics of delayed ventricular conduction. ConclusionsLoss of PFKFB2 results in metabolic remodeling marked by cardiac ancillary pathway activation. This could delineate an underpinning of pathologic changes to mechanical and electrical function in the heart. Clinical PerspectiveO_ST_ABSWhat is New?C_ST_ABSO_LIWe have generated a novel cardiomyocyte-specific knockout model of PFKFB2, the cardiac isoform of the primary glycolytic regulator Phosphofructokinase-2 (cKO). C_LIO_LIThe cKO model demonstrates that loss of cardiac PFKFB2 drives metabolic reprogramming and shunting of glucose metabolites to ancillary metabolic pathways. C_LIO_LIThe loss of cardiac PFKFB2 promotes electrophysiological and functional remodeling in the cKO heart. C_LI What are the Clinical Implications?O_LIPFKFB2 is degraded in the absence of insulin signaling, making its loss particularly relevant to diabetes and the pathophysiology of diabetic cardiomyopathy. C_LIO_LIChanges which we observe in the cKO model are consistent with those often observed in diabetes and heart failure of other etiologies. C_LIO_LIDefining PFKFB2 loss as a driver of cardiac pathogenesis identifies it as a target for future investigation and potential therapeutic intervention. C_LI

physiology↗

bioRxiv2023

17α-estradiol Alleviates High-Fat Diet-Induced Inflammatory and Metabolic Dysfunction in Skeletal Muscle of Male and Female Mice

Skeletal muscle has a central role in maintaining metabolic homeostasis. 17-estradiol (17-E2), a naturally-occurring non-feminizing diastereomer of 17{beta}-estradiol that demonstrates efficacy for improving metabolic outcomes in male, but not female, mice. Despite several lines of evidence showing that 17-E2 treatment improves metabolic parameters in middle-aged obese and old male mice through effects in brain, liver, and white adipose tissue little is known about how 17-E2 alters skeletal muscle metabolism, and what role this may play in mitigating metabolic declines. Therefore, this study aimed to determine if 17-E2 treatment improves metabolic outcomes in skeletal muscle from obese male and female mice following chronic high fat diet (HFD) administration. We hypothesized that male, but not female, mice, would benefit from 17-E2 treatment during HFD. To test this hypothesis, we used a multi-omics approach to determine changes in lipotoxic lipid intermediates, metabolites, and proteins related to metabolic homeostasis. In male mice, we show that 17-E2 alleviates HFD-induced metabolic detriments of skeletal muscle by reducing the accumulation of diacylglycerol (DAGs) and ceramides, inflammatory cytokine levels, and reduced the abundance of most of the proteins related to lipolysis and beta-oxidation. In contrast to males, 17-E2 treatment in female mice had little effect on the DAGs and ceramides content, muscle inflammatory cytokine levels, or changes to the relative abundance of proteins involved in beta-oxidation. These data support to the growing evidence that 17-E2 treatment could be beneficial for overall metabolic health in male mammals.

physiology↗

bioRxiv2020

Sirt5 deficiency causes post-translational protein malonylation and dysregulated cellular metabolism in chondrocytes under obesity conditions

ObjectiveObesity accelerates the development of osteoarthritis (OA) during aging and is associated with altered chondrocyte cellular metabolism. The objective of this study was to investigate the role of sirtuin 5 (SIRT5) in regulating chondrocyte protein lysine malonylation (MaK) and cellular metabolism under obesity-related conditions. MethodsMaK and SIRT5 were immunostained in knee articular cartilage of obese db/db mice and different aged C57BL6 mice with or without destabilization of the medial meniscus (DMM) surgery to induce OA. Primary chondrocytes were isolated from 7-day-old WT and Sirt5-/- mice and treated with varying concentrations of glucose and insulin to mimic obesity. Sirt5-dependent effects on MaK and metabolism were evaluated by Western blot, Seahorse Respirometry, and gas/chromatography-mass/spectrometry (GC-MS) metabolic profiling. ResultsMaK was significantly increased in cartilage of db/db mice and in chondrocytes treated with high concentrations of glucose and insulin (GluhiInshi). Sirt5 protein was increased in an age-dependent manner following joint injury, and Sirt5 deficient primary chondrocytes had increased MaK, decreased glycolysis rate, and reduced basal mitochondrial respiration. GC-MS identified 41 metabolites. Sirt5 deficiency altered 13 distinct metabolites under basal conditions and 18 metabolites under GluhiInshi treatment. Pathway analysis identified a wide range of Sirt5-dependent altered metabolic pathways that include amino acid metabolism, TCA cycle, and glycolysis. ConclusionThis study provides the first evidence that Sirt5 broadly regulates chondrocyte metabolism. We observed changes in Sirt5 and MaK levels in cartilage with obesity and joint injury, suggesting that the Sirt5-MaK pathway may contribute to altered chondrocyte metabolism that occurs during OA development.

cell biology↗

bioRxiv2017

Persistent homology demarcates a leaf morphospace

Current morphometric methods that comprehensively measure shape cannot compare the disparate leaf shapes found in seed plants and are sensitive to processing artifacts. We explore the use of persistent homology, a topological method applied across the scales of a function, to overcome these limitations. The described method isolates subsets of shape features and measures the spatial relationship of neighboring pixel densities in a shape. We apply the method to the analysis of 182,707 leaves, both published and unpublished, representing 141 plant families collected from 75 sites throughout the world. By measuring leaves from throughout the seed plants using persistent homology, a defined morphospace comparing all leaves is demarcated. Clear differences in shape between major phylogenetic groups are detected and estimates of leaf shape diversity within plant families are made. This approach does not only predict plant family, but also the collection site, confirming phylogenetically invariant morphological features that characterize leaves from specific locations. The application of a persistent homology method to measure leaf shape allows for a unified morphometric framework to measure plant form, including shape and branching architectures.

plant biology↗