A5071636149- Mitochondrial Function and Pathology
- DNA Repair Mechanisms
- Metabolism and Genetic Disorders
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- ATP Synthase and ATPases Research
- Cancer, Hypoxia, and Metabolism
- Genetic Neurodegenerative Diseases
- Carcinogens and Genotoxicity Assessment
- DNA and Nucleic Acid Chemistry
- Adipose Tissue and Metabolism
- Retinal Development and Disorders
- Amino Acid Enzymes and Metabolism
- Cancer-related gene regulation
- Metabolomics and Mass Spectrometry Studies
- Drug Transport and Resistance Mechanisms
- Retinal Diseases and Treatments
- Muscle Physiology and Disorders
- Muscle metabolism and nutrition
- Bacterial Genetics and Biotechnology
- Genetics and Neurodevelopmental Disorders
- RNA Research and Splicing
- Neurogenesis and neuroplasticity mechanisms
- Cancer Cells and Metastasis
- CRISPR and Genetic Engineering
University of Oslo
2016-2025
Oslo University Hospital
2016-2025
Weatherford College
2021
Mayo Clinic
2005
Massachusetts Institute of Technology
2001
Norwegian Defence Research Establishment
1992
Norwegian University of Science and Technology
1983
Recent data in invertebrates demonstrated that huntingtin (htt) is essential for fast axonal trafficking. Here, we provide direct and functional evidence htt involved trafficking mammals. Moreover, expression of full-length mutant (mhtt) impairs vesicular mitochondrial mammalian neurons vitro whole animals vivo. Particularly, mitochondria become progressively immobilized stop more frequently from transgenic animals. These defects occurred early development prior to the onset measurable...
Differentiation of neural stem cells (NSCs) involves the activation aerobic metabolism, which is dependent on mitochondrial function. Here, we show that differentiation NSCs robust increases in mass, DNA (mtDNA) copy number, and respiration capacity. The increased activity renders mtDNA vulnerable to oxidative damage, defective for 8-oxoguanine glycosylase (OGG1) function accumulate damage during differentiation. accumulated damages ogg1(-/-) inhibit normal maturation mitochondria manifested...
The mitochondrial DNA (mtDNA) of neural stem cells (NSCs) is vulnerable to oxidation damage. Subtle manipulations the cellular redox state affect mtDNA integrity in addition regulating NSC differentiation lineage, suggesting a molecular link between and regulation differentiation. Here we show that 8-oxoguanine glycosylase (OGG1) essential for repair damage viability during oxidative stress. Differentiating from <i>ogg1</i><sup>−/−</sup> knock-out mice spontaneously accumulate concomitantly...
One gene locus on chromosome I in Saccharomyces cerevisiae encodes a protein (YAB5_YEAST; accession no. P31378) with local sequence similarity to the DNA repair glycosylase endonuclease III from Escherichia coli. We have analyzed function of this gene, now assigned NTG1 (endonuclease three-like 1), by cloning, mutant analysis, and expression E. Targeted disruption produces that is sensitive H2O2 menadione, indicating required for oxidative damage vivo. Northern blot analysis studies...
Endonuclease III from Escherichia coli is the prototype of a ubiquitous DNA repair enzyme essential for removal oxidized pyrimidine base damage. The yeast genome project has revealed presence two genes in Saccharomyces cerevisiae,NTG1 and NTG2, encoding proteins with similarity to endonuclease III. Both contain highly conserved helix-hairpin-helix motif, whereas only one (Ntg2) harbors characteristic iron-sulfur cluster family. We have characterized these gene functions by mutant analysis as...
The oxidation resistance gene 1 (OXR1) prevents oxidative stress-induced cell death by an unknown pathway. Here, depletion of human OXR1 (hOXR1) sensitized several lines to hydrogen peroxide-induced stress, reduced mtDNA integrity, and increased apoptosis. In contrast, hOXR1 in cells lacking showed no significant change ROS or viability, suggesting that intracellular increase stress levels avoid a vicious cycle damage formation. Furthermore, expression p21 the antioxidant genes GPX2 HO-1 was...
Abstract The oxidation resistance gene 1 ( OXR1 ) is crucial for protecting against oxidative stress; however, its molecular function unknown. We employed RNA sequencing to examine the role of human genome wide transcription regulation. In total, in non-treated and hydrogen peroxide exposed HeLa cells, depletion resulted down-regulation 554 genes up-regulation 253 genes. These differentially expressed include factors (i.e. HIF1A , SP6, E2F8 TCF3 ), antioxidant PRDX4 PTGS1 CYGB numerous p53...
Huntington's disease (HD) is a progressive neurodegenerative disorder primarily affecting the basal ganglia and caused by expanded CAG repeats in huntingtin gene. Except for sizing, mitochondrial nuclear DNA (mtDNA nDNA) parameters have not yet proven to be representative biomarkers future therapy. Here, we identified general suppression of genes associated with aerobic metabolism peripheral blood mononuclear cells (PBMCs) from HD patients compared controls. In HD, complex II subunit SDHB...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOxidation of Thymine to 5-Formyluracil in DNA: Mechanisms Formation, Structural Implications, and Base Excision by Human Cell Free ExtractsSvein Bjelland, Lars Eide, Rune W. Time, Roland Stote, Ingrid Eftedal, Gunnar Volden, Erling SeebergCite this: Biochemistry 1995, 34, 45, 14758–14764Publication Date (Print):November 1, 1995Publication History Published online1 May 2002Published inissue 1 November...
Cockayne syndrome (CS) is a complex, progressive disease that involves neurological and developmental impairment premature aging. The majority of CS patients have mutations in the CSB gene. protein involved multiple DNA repair pathways mutated cells are sensitive to broad spectrum genotoxic agents. We tested hypothesis sensitivity such genotoxins could be mediated by mitochondrial dysfunction as consequence mutation. mtDNA from csb(m/m) mice accumulates oxidative damage including...
Cardiac mitochondrial dysfunction has been implicated in heart failure of diverse etiologies. Generalized disease also leads to cardiomyopathy with various clinical manifestations. Impaired homeostasis may over time, such as the aging heart, lead cardiac dysfunction. Mitochondrial DNA (mtDNA), close electron transport chain and unprotected by histones, be a primary pathogenetic site, but this is not known. Here, we test hypothesis that cumulative damage cardiomyocyte mtDNA failure....
Ogg1 and Mutyh DNA glycosylases cooperate to prevent mutations caused by 8-oxoG, a major premutagenic lesion associated with cognitive decline. We have examined behavior function in mice deficient of these glycosylases. Ogg1−/−Mutyh−/− were more active less anxious, impaired learning ability. In contrast, Mutyh−/− showed moderately improved memory. observed no apparent change genomic 8-oxoG levels, suggesting that play minor roles global repair adult brain. Notably, transcriptome analysis...
Abstract Production of mitochondrial reactive oxygen species and integrity DNA (mtDNA) are crucial in breast cancer progression metastasis. Therefore, we evaluated the role mtDNA damage by genetically modulating repair enzyme 8-oxoguanine glycosylase (OGG1) PyMT transgenic mouse model mammary tumorigenesis. We generated mice lacking OGG1 (KO), overexpressing human subunit 1α mitochondria (Tg), simultaneously (KO/Tg). found that Tg KO/Tg developed significantly smaller tumors than KO...
Oxidative phosphorylation involves a complex multi-enzymatic mitochondrial machinery critical for proper functioning of the cell, and defects herein cause wide range diseases called "primary disorders" (PMDs). Mutations in about 400 nuclear 37 genes have been documented to PMDs, which an estimated birth prevalence 1:5000. Here, we describe 4-year-old female presenting from early childhood with psychomotor delay white matter signal changes affecting several brain regions, including brainstem,...
Mitochondrial dysfunction underlying changes in neurodegenerative diseases is often associated with apoptosis and a progressive loss of neurons, damage to the mitochondrial genome proposed be involved such pathologies. In present study we designed mouse model that allows us specifically induce DNA toxicity forebrain neurons adult mice. This achieved by CaMKIIalpha-regulated inducible expression mutated version UNG repair enzyme (mutUNG1). capable removing thymine from genome. We demonstrate...
Reducing mtDNA content was considered as a critical step in the metabolism restructuring for cell stemness restoration and further neoplastic development. However, connections between depletion reprograming-based cancer prostate cancers are still lack of studies. Here, we demonstrated that human CRPC line PC3 tolerated high concentration replication inhibitor ethidium bromide (EtBr) triggered universal metabolic remodeling process. Failure completing process caused lethal consequences. The...