Marina Serrano‐Maciá
A5036874399- Liver Disease Diagnosis and Treatment
- Ubiquitin and proteasome pathways
- Diet, Metabolism, and Disease
- Endoplasmic Reticulum Stress and Disease
- Liver Disease and Transplantation
- Cancer, Hypoxia, and Metabolism
- Drug-Induced Hepatotoxicity and Protection
- Peptidase Inhibition and Analysis
- Liver physiology and pathology
- RNA modifications and cancer
- Pancreatic function and diabetes
- Folate and B Vitamins Research
- COVID-19 Clinical Research Studies
- Diet and metabolism studies
- Magnesium in Health and Disease
- Gut microbiota and health
- Alcohol Consumption and Health Effects
- Drug Transport and Resistance Mechanisms
- Heat shock proteins research
- SARS-CoV-2 and COVID-19 Research
- Ferroptosis and cancer prognosis
- Pediatric Hepatobiliary Diseases and Treatments
- Hepatocellular Carcinoma Treatment and Prognosis
- Trace Elements in Health
- Pharmacogenetics and Drug Metabolism
CIC bioGUNE
2018-2025
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
2018-2023
Inserm
2023
Université de Montpellier
2023
Institut de Recherche en Cancérologie de Montpellier
2023
Institut Regional du Cancer de Montpellier
2023
Boeing (Spain)
2022
Universitat de Miguel Hernández d'Elx
2019-2021
Background and Aims: Recent studies suggest that mitochondrial dysfunction promotes progression to NASH by aggravating the gut‐liver status. However, underlying mechanism remains unclear. Herein, we hypothesized enhanced activity might reshape a specific microbiota signature that, when transferred germ‐free (GF) mice, could delay progression. Approach Results: Wild‐type methylation‐controlled J protein knockout (MCJ‐KO) mice were fed for 6 weeks with either control or choline‐deficient,...
Neddylation is a post-translational mechanism that adds ubiquitin-like protein, namely neural precursor cell expressed developmentally downregulated protein 8 (NEDD8). Here, we show neddylation in mouse liver modulated by nutrient availability. Inhibition of reduces gluconeogenic capacity and the hyperglycemic actions counter-regulatory hormones. Furthermore, people with type 2 diabetes display elevated hepatic levels. Mechanistically, fasting or caloric restriction mice leads to...
Hepatic ischemia-reperfusion injury (IRI) is the leading cause of early posttransplantation organ failure as mitochondrial respiration and ATP production are affected. A shortage donors has extended liver donor criteria, including aged or steatotic livers, which more susceptible to IRI. Given lack an effective treatment extensive transplantation waitlist, we aimed at characterizing effects accelerated activity by silencing methylation-controlled J protein (MCJ) in three preclinical models...
Ubiquitin and ubiquitin-like chains are finely balanced by conjugating de-conjugating enzymes. Alterations in this balance trigger the response to stress conditions often observed pathologies. How such changes detected is not well understood. We identify HSP70 chaperone as a sensor of between mono- poly-NEDDylation. Upon DNA damage, induction de-NEDDylating enzyme NEDP1 restricts formation NEDD8 chains, mainly through lysines K11/K48. This promotes APAF1 oligomerization apoptosis induction,...
Neddylation is a druggable and reversible ubiquitin-like post-translational modification upregulated in many diseases, including liver fibrosis, hepatocellular carcinoma, more recently, non-alcoholic fatty disease (NAFLD). Herein, we propose to address the effects of neddylation inhibition underlying mechanisms pre-clinical models NAFLD.Hepatic measured by immunohistochemical analysis NEDD8 serum levels ELISA assay were evaluated NAFLD clinical samples. The using pharmacological small...
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a multi-organ damage that includes hepatic dysfunction, which has been observed in over 50% of COVID-19 patients. Liver injury could be attributed to the cytopathic effects, exacerbated immune responses or treatment-associated drug toxicity. Herein we demonstrate hepatocytes are susceptible infection different models: primary derived from humanized angiotensin-converting enzyme-2 mice (hACE2) and human hepatocytes....
Non-alcoholic fatty liver disease (NAFLD) is a complex pathology in which several dysfunctions, including alterations metabolic pathways, mitochondrial functionality and unbalanced lipid import/export, lead to accumulation progression inflammation fibrosis. The enzyme glycine N-methyltransferase (GNMT), the most important implicated S-adenosylmethionine catabolism liver, downregulated during NAFLD progression. We have studied mechanism involved GNMT downregulation by its repressor microRNA...
•CNNM4 acts as a magnesium exporter in the liver. Its upregulation NASH leads to elevated levels serum.•Liver-specific CNNM4 targeting alleviates steatosis, inflammation, and fibrosis preclinical models.•siRNA-mediated downregulation promotes hepatic accumulation reduces endoplasmic reticulum stress.•Silencing enhances microsomal triglyceride transfer protein activity leading VLDL assembly secretion. Background & AimsPerturbations of intracellular (Mg2+) homeostasis have implications for...
Abstract Acetaminophen overdose is one of the leading causes acute liver failure and transplantation in Western world. Magnesium essential several cellular processess. The Cyclin M family involved magnesium transport across cell membranes. Herein, we identify that among all transporters, only M4 expression upregulated patients with acetaminophen overdose, disturbances serum levels. In liver, interferes mitochondrial reservoir via M4, affecting ATP production reactive oxygen species...
Cholangiocarcinoma (CCA) comprises a heterogeneous group of malignant tumors associated with dismal prognosis. Alterations in post-translational modifications (PTMs), including NEDDylation, result abnormal protein dynamics, cell disturbances and disease. Herein, we investigate the role NEDDylation CCA development progression.Levels functions together response to pevonedistat (NEDDylation inhibitor) or CRISPR/Cas9 against NAE1 were evaluated vitro, vivo and/or patients CCA. The preneoplastic...
Background and Aims: Alcohol-associated liver disease (ALD) accounts for 70% of liver-related deaths in Europe, with no effective approved therapies. Although mitochondrial dysfunction is one the earliest manifestations alcohol-induced injury, restoring activity remains a problematic strategy due to oxidative stress. Here, we identify methylation-controlled J protein (MCJ) as mediator ALD progression hypothesize that targeting MCJ may help recovering fitness without collateral damage....
Abstract NEDDylation is a post-translational modification whereby the ubiquitin-like molecule NEDD8 attached to protein substrates in process dependent on activating enzyme regulatory subunit (NAE1). emerging as regulator of cancer biology, but its precise role antitumor immunity has not been thoroughly characterized. Here, we study impact CD8+ T cell–mediated responses. Analysis publicly available single-cell RNA sequencing databases revealed that tumor-infiltrating lymphocytes (TILs)...
BACKGROUNDArachidyl amido cholanoic acid (Aramchol) is a potent downregulator of hepatic stearoyl-CoA desaturase 1 (SCD1) protein expression that reduces liver triglycerides and fibrosis in animal models steatohepatitis.In phase IIb clinical trial patients with nonalcoholic steatohepatitis (NASH), 52 wk treatment Aramchol reduced blood levels glycated hemoglobin A1c, an indicator glycemic control. AIMTo assess lipid glucose metabolism mouse hepatocytes NASH model [induced 0.1% methionine...
There has been an intense focus to uncover the molecular mechanisms by which fasting triggers adaptive cellular responses in major organs of body. Here, we show that mice, hepatic S-adenosylmethionine (SAMe)-the principal methyl donor-acts as a metabolic sensor nutrition fine-tune catabolic-fasting response modulating phosphatidylethanolamine N-methyltransferase (PEMT) activity, endoplasmic reticulum-mitochondria contacts, β-oxidation, and ATP production liver, together with FGF21-mediated...
Liver fibrosis is the excessive accumulation of extracellular matrix proteins that occurs in chronic liver disease. Ubiquitination a post-translational modification crucial for plethora physiological processes. Even though ubiquitin system has been implicated several human diseases, role ubiquitination remains poorly understood. Here, multi-omics approaches were used to address this. Untargeted metabolomics showed carbon tetrachloride (CCl4)-induced promotes changes hepatic metabolome,...
Background and Aims: Alcohol-related liver disease (ALD) is a leading cause of liver-related mortality worldwide, with limited treatment options beyond abstinence transplantation. Chronic alcohol consumption has been linked to magnesium (Mg 2+ ) deficiency, which can influence the progression. The mechanisms underlying Mg homeostasis dysregulation in ALD remain elusive. This study aimed investigate role transporter Cyclin M4 (CNNM4) by analyzing its expression patterns patients preclinical...
Mitochondria are the major organelles for formation of reactive oxygen species (ROS) in cell, and mitochondrial dysfunction has been described as a key factor pathogenesis cholestatic liver disease. The methylation-controlled J-protein (MCJ) is protein that interacts with represses function complex I electron transport chain. relevance MCJ pathology cholestasis not yet explored.We studied relationship between cholestasis-induced injury biopsies from patients chronic diseases, livers primary...