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Abstract: Hibernating brown bears, due to a drastic reduction in metabolic rate, show only moderate muscle wasting. Here, we evaluate if ATPase activity of resting skeletal muscle myosin can contribute to this energy sparing. By analyzing single muscle fibers taken from the samebears,eitherduring hibernationorin summer,wefindthatfibersfromhibernatingbearshaveamilddeclineinforce production and a significant reduction in ATPase activity. Single fiber proteomics, western blotting, and immunohistochemical analyses reveal major remodeling of the mitochondrial proteome during hibernation. Furthermore, using bioinformatical approaches and western blotting we find that phosphorylated myosin light chain, a known stimulator of basal myosin ATPase activity, is decreased in hibernating and disused muscles. These results suggestthatskeletalmusclelimitsenergylossbyreducingmyosinATPaseactivity, indicating a possible role for myosin ATPase activity modulation in multiple muscle wasting conditions.
Keywords: translational research, animal physiology, metabolism
Published in DiRROS: 14.01.2026; Views: 163; Downloads: 94
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Abstract: Background: Pathogenic hemizygous variants in ATP7A most commonly cause Menkes disease or occipital horn syndrome (OHS), whereas ATP7A-related distal hereditary motor neuropathy (dHMN) is rarely reported. Here, we describe two adult brothers with an overlapping dHMN/OHS phenotype caused by a novel ATP7A splice-site variant and review the clinical and genetic features of previously published patients with ATP7Arelated dHMN. Methods: We performed detailed clinical, electrophysiological, and genetic evaluations of both siblings, including exome sequencing and RNA analysis. Additionally, we reviewed the clinical, electrophysiological, and genetic data of previously reported patients with ATP7A-related dHMN. Results: We identified a novel hemizygous ATP7A splice-site variant (NM_000052.7:c.1544-2A>T) in both brothers. The younger brother, who exhibited a more severe phenotype, presented in early childhood with mild global developmental delay, intellectual disability, and chronic diarrhea, while the older brother had childhood-onset chronic diarrhea without cognitive impairment. Both developed distal hereditary motor neuropathy later in life, and imaging revealed occipital horns. Serum copper and ceruloplasmin levels were mildly reduced. RNA sequencing revealed two aberrant transcript isoforms resulting from the splice-site variant, one of which may produce a partially functional protein. Review of previously reported patients shows that ATP7A-related dHMN may occur isolated or with overlapping features of OHS. In patients with the overlapping phenotype, chronic diarrhea was often the first symptom, followed by slowly progressive dHMN. Conclusions: Previously reported ATP7A-related dHMN has been mostly associated with missense variants. Our findings expand the mutational spectrum by identifying a splice-site variant. In patients with an overlapping OHS/dHMN phenotype, diagnosis was typically delayed for decades, suggesting this presentation remains underdiagnosed.
Keywords: ATP7A, splice-site variant, distal hereditary motor neuropathy, occipital horn syndrome, copper metabolism, neurogenetics
Published in DiRROS: 05.12.2025; Views: 628; Downloads: 142
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Abstract: Background. Yarrowia lipolytica is a promising host for sustainable microbial oil production from waste-derived carboxylic acids such as acetate and propionate. Nonetheless, the molecular mechanisms underlying the metabolism and assimilation of these substrates, particularly under nitrogen limitation, are still not fully understood. Results. We conducted a multi-condition transcriptomic analysis of Y. lipolytica strain EXF-17398 under nitrogen-limiting conditions to investigate its transcriptional adaptation to acetate and propionate utilisation. Our results revealed distinct transcriptional responses associated with metabolic adaptation, including the coordinated regulation of Jen and Gpr carboxylate transporter families, suggesting a dual system for carboxylate uptake. JEN5 and GPR1 appear central to propionate and acetate utilisation, respectively. Our data suggest that propionate toxicity is mitigated through its conversion via the methylcitrate cycle and potentially the malonate semialdehyde pathway, preventing accumulation of cytotoxic propionyl-CoA in the cytosol. The upregulation of carnitine acyltransferases suggests active mitochondrial transport of acyl-CoAs, linking detoxification with energy metabolism. Under tested conditions, the de novo lipid synthesis was consistent with carbon overflow from acetyl-CoA and propionyl-CoA, supported by intracellular nitrogen recycling and redox balancing, independent of classical nitrogen regulatory pathways. Conclusions. These findings illustrate the capacity of Y. lipolytica to coordinate carbon and nitrogen metabolism during carboxylate utilisation, such as acetate and propionate, offering insights to guide the optimisation of microbial oil production from renewable feedstocks.
Keywords: propionate, transport, metabolism
Published in DiRROS: 21.11.2025; Views: 299; Downloads: 159
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Abstract: Understanding the molecular mechanisms behind plant response to stress can enhancebreeding strategies and help us design crop varieties with improved stress tolerance,yield, and quality. To investigate resource redistribution from growth- to defense-relatedprocesses in an essential tuber crop, potato, here we generate a large-scale compartmen-talized genome-scale metabolic model (GEM), potato-GEM. Apart from a large-scalereconstruction of primary metabolism, the model includes the full known potato sec-ondary metabolism, spanning over 566 reactions that facilitate the biosynthesis of 182distinct potato secondary metabolites. Constraint-based modeling identifies that theactivation of the largest amount of secondary (defense) pathways occurs at a decreaseof the relative growth rate of potato leaf, due to the costs incurred by defense. We thenobtain transcriptomics data from experiments exposing potato leaves to two bioticstress scenarios, a herbivore and a viral pathogen, and apply them as constraints toproduce condition-specific models. We show that these models recapitulate experimen-tally observed decreases in relative growth rates under treatment as well as changes inmetabolite levels between treatments, enabling us to pinpoint the metabolic rewiringunderlying growth–defense trade-offs. Potato- GEM thus presents a useful resource tostudy and broaden our understanding of potato and general plant defense responsesunder stress conditions.
Keywords: systems biology, constraint-based metabolic modeling, growth-defence trade-offs, secondary metabolism
Published in DiRROS: 24.09.2025; Views: 580; Downloads: 217
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Abstract: Research on the metabolic physiology of groundwater species, particularly regarding oxygen consumption rates (OCR), has made significant advancement, revealing valuable insights into the adaptations of exclusively groundwater-dwelling (stygobitic) species. However, a comprehensive understanding of how these metabolic rates scale with body mass and respond to temperature changes remains elusive. This study aims to bridge this gap by reviewing published data on OCR across a variety of groundwater organisms to elucidate patterns of metabolic rates in relation to body size and temperature. We employed a combination of literature review and quantitative analyses, focusing on the allometric scaling of OCR with body weight and the effect of temperature on metabolic rates. Our findings indicate that OCR scales with body weight in an allometric pattern, with an inter-species slope of 0.80, suggesting non-isometric scaling. Furthermore, our analysis showed that stygobitic species’ metabolic rates are less responsive to warming than those of non-stygobitic species at low to moderate temperatures. However, at higher temperatures, metabolic rates in stygobitic species decline faster than in non-stygobitic taxa, highlighting a potential vulnerability to global climate change. This study contributes to our understanding of the metabolic strategies of groundwater species, underscoring the need for further research to fully grasp the eco-evolutionary implications of these findings for groundwater conservation.
Keywords: allometry, Arrhenius equation, ectotherms, metabolism, oxygen consumption rate, respiration, stygobiont
Published in DiRROS: 13.09.2024; Views: 1035; Downloads: 712
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