Biology subjects

Olin, M.

Publications and source records attributed to Olin, M..

4 recordsLinked to original sources

bioRxiv2025

Mitochondrial Dysfunction Induces Hepatic Lipid Accumulation and Inflammatory Responses in mtDNA Mutator Mice

BackgroundNon-Alcoholic Fatty Liver Disease (NAFLD), now referred to as Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), is a widespread and complex health issue characterized by the accumulation of lipids in liver cells, not linked to alcohol consumption or other known liver problems. Despite its strong association with insulin resistance and obesity, a notable proportion of lean individuals develop NAFLD, suggesting the involvement of additional factors. Mitochondrial dysfunction has emerged as a potential contributor, given its role in lipid homeostasis and the generation of reactive oxidative species (ROS). MethodsIn this study, we took advantage of the mtDNA mutator mouse model, characterized by oxidative phosphorylation deficiency due to accelerated accumulation of mitochondrial DNA (mtDNA) mutations, to investigate how mitochondrial dysfunction affects liver homeostasis triggering fat accumulation. ResultsWe found that mitochondrial dysfunction induces liver steatosis and inflammation in this mouse model at a young age, independent of obesity. Using quantitative mass spectrometry, we reveal that mitochondrial dysfunction alters the levels of multiple proteins involved in lipid metabolism, cholesterol homeostasis, and inflammation. In vitro data show a shift in cellular metabolism toward the glycolytic pathway and confirm the upregulation of inflammatory genes. These changes are associated with oxidative stress and occur independently of mtDNA molecule release into the cytoplasm. ConclusionOur findings demonstrate that liver steatosis might develop as result of mitochondrial dysfunction without obesity and insulin resistance, underscoring the importance of mitochondrial dysfunction in NAFLD development in lean individuals and providing valuable insights into the molecular mechanisms underlying this complex metabolic disorder. This mouse model offers a unique platform for further investigations aimed at unraveling the intricacies of NAFLD pathogenesis and potential therapeutic targets beyond conventional risk factors.

cell biology↗

bioRxiv2024

CD200 depletion in glioma enhances antitumor immunity and induces tumor rejection

High-grade gliomas are a major health challenge with poor prognosis and high morbidity. Immune-checkpoint inhibitors (ICI) have emerged as promising therapeutic options for several malignancies yet show little efficacy against central nervous system (CNS) tumors. CD200 is a newly recognized immune checkpoint that modulates immune homeostasis. CD200 protein is expressed by a variety of cells, including immune cells and stromal cells, and is overexpressed by many tumors. The shedding of CD200 from tumor cells can create an immunosuppressive environment that dampens anti-tumor immunity by modulating cytolytic activity and cytokine expression both within and outside the tumor microenvironment (TME). While it is well-accepted that CD200 induces a pro-tumorigenic environment through its ability to suppress the immune response, we sought to determine the role of glioma-specific expression of CD200. We show that CD200 is expressed across glioma types, is shed from tumor cells, and increases over time in the serum of patients undergoing immunotherapy. Using CD200 knockout (KO) glioma models, we demonstrated that glioma cell-derived CD200 promotes tumor growth in vivo and in vitro. Notably, CD200 KO gliomas are spontaneously rejected by their host, a process that required a fully functional immune system, including NK and T-cells. Moreover, we report that glioma-derived or brain-injected soluble CD200 contributes to the suppression of antigen-specific CD8 T-cells in the draining lymph nodes (dLNs). Our work provides new mechanistic insights regarding CD200-mediated immunosuppression by gliomas. Statement of significanceWe demonstrate mechanisms of the druggable glioma-derived CD200 checkpoint on tumor growth and immune suppression.

immunology↗

bioRxiv2024

Titration-WB: A methodology for accurate quantitative protein determination overcoming reproducibility errors

Western blot (WB) technique is widely used to identify and quantify proteins in biological samples, but it is poorly accurate and precise for quantitative purposes. Merging the WB with the titration assay, we established a reliable method for protein quantification based on the slope of the linear function for signal-intensity/total protein loaded. Titration-WB unravels systematic and operator errors, compensates for problems in antibody affinity/avidity, and permits trustworthy inter-WB comparison.

biochemistry↗

bioRxiv2022

Status and future perspectives for pikeperch (Sander lucioperca) stocks in Europe

Pikeperch (Sander lucioperca) is a European fresh and brackish water piscivorous fish, important as both a key predator and a valuable commercial and recreational fisheries species. There are concerns that some stocks are depleted due to overfishing and environmental changes. We review data collection and population assessments currently used for nine pikeperch stocks across six European countries and apply a unified assessment framework to evaluate population status and trends. For this we first standardised commercial, scientific, and recreational catch-per-unit-effort (CPUE) and catch time series and then applied Bayesian surplus production models. Our results showed that three stocks (including two in the Baltic Sea) were strongly depleted, with estimated biomasses considerably lower than the biomass at maximum sustainable yield (Bmsy). Other stocks were either close or higher than their estimated Bmsy. Looking at the trends, we find that four stocks (Lake Oulujarvi, Kvadofjarden, Lake Peipsi and Lipno) showed increasing biomass trends and two (Curonian Lagoon, Galtfjarden) had a strong decline in biomass. In most cases the stocks with clear signs of recovery were also those for which strong management strategies have been implemented. We find that, despite pikeperch being one of the most valuable inland fisheries, formalised stock assessments and regular surveys remain rare. Importantly, although most stocks are strongly targeted by recreational fishing, estimates of recreational catch are highly uncertain. We conclude that data limited stock assessment methods are useful for assessing fish population status and highlight an urgent need to improve pikeperch scientific monitoring and assessment of recreational catches.

ecology↗