Margret H OgmundsdottirUniversity of Iceland | HI · Biomedical Center
Margret H Ogmundsdottir
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72
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Introduction
Skills and Expertise
Publications
Publications (72)
Macroautophagy/autophagy is an essential catabolic process that targets a wide variety of cellular components including proteins, organelles, and pathogens. ATG7, a protein involved in the autophagy process, plays a crucial role in maintaining cellular homeostasis and can contribute to the development of diseases such as cancer. ATG7 initiates auto...
PINK1, mutated in familial forms of Parkinson's disease, initiates mitophagy following mitochondrial depolarization. However, it is difficult to monitor this pathway physiologically in mice as loss of PINK1 does not alter basal mitophagy levels in most tissues. To further characterize this pathway in vivo, we used mito-QC mice in which loss of PINK...
PINK1, mutated in familial forms of Parkinson's disease, initiates mitophagy following mitochondrial depolarization. However, it is difficult to monitor this pathway physiologically in mice as loss of PINK1 does not alter basal mitophagy levels in most tissues. To further characterize this pathway in vivo, we used mito-QC mice in which loss of PINK...
The E1-like enzyme ATG7 belongs to a group of ATG proteins that mediate the autophagy process. Autophagy is a highly conserved degradation pathway important for maintaining homeostasis in eukaryotic cells. Here, we study the evolution of E1 enzymes and specifically describe a region of ATG7 that emerged early in vertebrates. This vertebrate-specifi...
Autophagy is a housekeeping mechanism tasked with eliminating misfolded proteins and damaged organelles to maintain cellular homeostasis. Autophagy deficiency results in increased oxidative stress, DNA damage and chronic cellular injury. Among the core genes in the autophagy machinery, ATG7 is required for autophagy initiation and autophagosome for...
Aroylated phenylenediamines (APDs) are novel modulators of innate immunity with respect to enhancing the expression of antimicrobial peptides and maintaining epithelial barrier integrity. Here, we present a new study on induction of autophagy in human lung epithelial cells by the APD HO53. Interestingly, HO53 affected autophagy in a dose-dependent...
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this
topic has received increasing attention, and many scientists have entered the field. Our knowledge base
and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular
basis updated guidelines for monit...
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this
topic has received increasing attention, and many scientists have entered the field. Our knowledge base
and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular
basis updated guidelines for monit...
The microphthalmia-associated transcription factor (MITF) is a critical regulator of melanocyte development and differentiation. It also plays an important role in melanoma where it has been described as a molecular rheostat that, depending on activity levels, allows reversible switching between different cellular states. Here, we show that MITF di...
the PDF can be download freely on pubmed.
https://pubmed.ncbi.nlm.nih.gov/33634751/
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...
The MITF, TFEB, TFE3 and TFEC (MiT-TFE) proteins belong to the basic helix-loop-helix family of leucine zipper transcription factors. MITF is crucial for melanocyte development and differentiation, and has been termed a lineage-specific oncogene in melanoma. The three related proteins MITF, TFEB and TFE3 have been shown to be involved in the biogen...
The microphthalmia associated transcription factor (MITF) is a critical regulator of melanocyte development and differentiation. It also plays an important role in melanoma where it has been described as a molecular rheostat that, depending on activity levels, allows reversible switching between different cellular states. Here we show that MITF dir...
Dysregulated cholesterol homeostasis promotes the pathology of atherosclerosis, myocardial infarction and strokes. Cellular cholesterol is mainly regulated at the transcriptional level by SREBP2, but also through uptake of extracellular cholesterol from low density lipoproteins (LDL) via expression of LDL receptors (LDLR) at the cell surface. Ident...
Proton pump inhibitors (PPIs) are commonly used drugs among cancer patients. Due to conflicting reports on their safety, we aimed to determine whether PPI use is associated with mortality among prostate cancer patients. In this population-based cohort study, we identified incident diagnoses of prostate cancer between 2007 and 2012 (n = 1058). Follo...
Purpose
The microphthalmia‐associated transcription factor (Mitf) gene is crucial for development of the retinal pigment epithelium (RPE) and photoreceptors. Loss of function mutations in this gene can cause ocular hypopigmentation, microphthalmia and blindness. Mice heterozygous for the Mitfmi‐wh/+ mutation have been used as a model for Waardenbur...
Purpose
Mice carrying different mutations in the microphthalmia‐associated transcription factor (Mitf) gene, affect the normal the retinal pigment epithelium (RPE) resulting in microphthalmia. The MitfK243R/K243R; Tyr::Cre mice have an induced conditional mutation, where Lysine 243 is mutated to Arginine, thus affecting DNA binding. The purpose of...
Interrupted dimeric coiled coil segments are found in a broad range of proteins and generally confer selective functional properties such as binding to specific ligands. However, there is only one documented case of a basic-helix-loop-helix leucine zipper transcription factor-microphthalmia-associated transcription factor (MITF)-in which an inserti...
Cholangiocarcinoma is an aggressive cancer originating from the bile duct. Although cholangiocarcinoma does occur in families, to date no specific causative gene has been identified. We identified ATG7 as a cancer susceptibility gene using a joint genetic analysis of an extended pedigree with familial cholangiocarcinoma in combination with a popula...
The MITF, TFEB, TFE3 and TFEC (MiT-TFE) proteins belong to a larger family of basic helix-loop-helix leucine zipper transcription factors that are able to bind DNA and regulate gene expression. MITF is crucial for melanocyte development and has been called a lineage-specific oncogene in melanoma whereas its relatives TFEB and TFE3 are involved in t...
Mutations in the microphthalmia-associated transcription factor (Mitf) gene can cause retinal pigment epithelium (RPE) and retinal dysfunction and degeneration. We examined retinal and RPE structure and function in 3 month old mice homo- or heterozygous or compound heterozygous for different Mitf mutations (Mitfmi-vga9/+, Mitfmi-enu22(398)/Mitfmi-e...
The MITF transcription factor is a master regulator of melanocyte development and a critical factor in melanomagenesis. The related transcription factors TFEB and TFE3 regulate lysosomal activity and autophagy processes known to be important in melanoma. Here we show that MITF binds the CLEAR- box element in the promoters of lysosomal and autophago...
Purpose
Increased expression of Vacuolar‐type H⁺ ATPases (V‐ATPases), in the plasma membrane of cancer cells has been suggested to contribute to the development of aggressive cancer phenotypes by promoting acidic tumor microenvironments. Accumulating data suggest that proton pump inhibitors (PPIs) may elicit a chemopreventive effect via V‐ATPase in...
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Autophagy is a degradation pathway important for cellular homeostasis. The E1-like enzyme ATG7 is a key component of the autophagy machinery, with the main function of mediating the lipidation of LC3/GABARAP during autophagosome formation. By analysing mRNA-sequencing data we found that in addition to the full-length ATG7 isoform, various tissues e...
Microphthalmia‐associated transcription factor (MITF) is a member of the basic helix‐loop‐helix leucine zipper (bHLH‐Zip) family and functions as the master regulator of the melanocytic lineage. MITF‐M is the predominant isoform expressed in melanocytes and melanoma cells and, unlike other MITF isoforms, it is constitutively nuclear. Mutational ana...
Background
The use of proton-pump inhibitors (PPIs) has grown worldwide, and there are concerns about increased unsubstantiated long-term use. The aim of the study was to describe the real-world use of PPIs over the past decade in an entire national population.
Methods
This was a nationwide population-based drug-utilization study. Patterns of outp...
Supplementary Material, supplementary_material – Proton-pump inhibitors among adults: a nationwide drug-utilization study
The mechanistic target of rapamycin complex 1 (mTORC1) is recruited to the lysosome by Rag guanosine triphosphatases (GTPases) and regulates anabolic pathways in response to nutrients.We found that MiT/TFE transcription factors-master regulators of lysosomal and melanosomal biogenesis and autophagy-control mTORC1 lysosomal recruitment and activity...
Purpose
Microphthalmia‐associated transcription factor (MITF) regulates the differentiation and development of the retinal pigment epithelium (RPE). Mice that lack functional MITF do not develop the RPE and have microphthalmia. Recent studies have involved MITF in autophagy regulation in other cell types. The purpose of this study was to examine if...
Purpose
The Mitf (microphthalmia-associated transcription factor) gene that is essential for the normal development of the retinal pigment epithelium (RPE). Mutations in this gene can cause hypopigmentation, microphthalmia and blindness. The purpose of this work was to analyze the retinal function and morphology in mice with specific Mitf mutations...
Autophagy is considered a therapeutic target in various cancer types, including melanoma. The transcription factors TFEB and TFE3 have been shown to play a key role in autophagy regulation in various cell types by affecting gene expression required for this process. A close relative to these factors is the transcription factor MITF; often termed th...
The v-ATPase is a fundamental eukaryotic enzyme central to cellular homeostasis. Although its impact on key metabolic regulators such as TORC1 is well-documented, our knowledge of mechanisms that regulate v-ATPase activity is limited. Here, we report that the Drosophila transcription factor Mitf is a master regulator of this holoenzyme. Mitf direct...
Lipoxygenases (LOXs) and their products are involved in several biological functions and have been associated with carcinogenesis. Protolichesterinic acid (PA), a lichen metabolite, inhibits 5- and 12-LOX and has anti-proliferative effects on various cancer cell lines. Here, PA was shown to inhibit proliferation of multiple myeloma cells, RPMI 8226...
Melanocytes and their precursor melanoblasts depend on the Microphthalmia-associated transcription factor (MITF) for most decisions, including specification, differentiation, function, survival and proliferation. MITF also plays an important role in melanoma where it is essential for maintaining tumor cell survival. As MITF plays multiple roles, it...
Autophagy is induced as a homeostatic process by energy shortage and cellular stress but can also be influenced by drugs. Poor autophagic function contributes to carcinogenesis but autophagy also promotes survival of tumours. We performed immunohistochemistry for LC3, pAMP kinase, p62, p53 on 15 samples from breast cancer and 14 from pancreatic can...
The vast amount of whole genome sequence information generated and made freely available in the last few years has opened a whole new avenue of genetic research. For example, genome wide association studies have highlighted the role of single nucleotide polymorphisms (SNPs) in various different phenotypic traits and chromatin immunoprecipitation se...
Sequence polymorphisms linked to human diseases and phenotypes in genome-wide association studies often affect noncoding regions. A SNP within an intron of the gene encoding Interferon Regulatory Factor 4 (IRF4), a transcription factor with no known role in melanocyte biology, is strongly associated with sensitivity of skin to sun exposure, freckle...
The basic-helix-loop-helix-leucine zipper (bHLHZip) protein MITF (microphthalmia-associated transcription factor) is a master regulator of melanocyte development. Mutations in MITF have been found in patients with the dominantly inherited hypopigmentation and deafness syndromes Waardenburg syndrome type 2A (WS2A) and Tietz syndrome (TS). Additional...
Low bone mineral density (BMD) is used as a parameter of osteoporosis. Genome-wide association studies of BMD have hitherto focused on BMD as a quantitative trait, yielding common variants of small effects that contribute to the population diversity in BMD. Here we use BMD as a dichotomous trait, searching for variants that may have a direct effect...
The lichen compound usnic acid (UA) is a lipophilic weak acid that acts as a proton shuttle and causes loss of mitochondrial inner membrane potential. In the current study we show that UA treatment induced the formation of autophagosomes in human cancer cells, but had minimal effects on normal human fibroblasts. However, autophagic flux was incompl...
UA induces formation of autophagosome vacuoles. LC3 puncta per cell were counted and quantified by ImageJ and data presented as 95% family-wise confidence level. (A) T47D cells treated with UA for 2 and 24 hours. (B) MCF7 cells treated with UA for 2 and 24 hours. (C) Normal human fibroblasts treated with UA for 2 and 24 hours. (D) An increase in LC...
UA does not cause apoptosis. (A) Cytochrome c leakage was not detectable, by immunofluorescense in T47D and Capan-2 cells after treatment with UA (10 µg/mL; DMSO 0.2%) for 24, 48 and 72 hours. (B) No cleavage products of Caspase-3 were detectable after treatment with UA (10 µg/mL; DMSO 0.2%) after 24, 48 and 72 hours. The scale bar shown represents...
UA does not lead to degradation of p62. No decrease in p62 immunoperoxidase staining was detected, in T47D cells after treatment with UA (10 µg/mL; DMSO 0.2%) for 24 hours. The scale bar shown represents 100 µm and applies to both panels.
(TIF)
Microphthalmia-associated transcription factor (MITF) is a master regulator of melanocyte development and an important oncogene in melanoma. MITF heterodimeric assembly with related basic helix-loop-helix leucine zipper transcription factors is highly restricted, and its binding profile to cognate DNA sequences is distinct. Here, we determined the...
Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL
The regulatory protein MITF (microphthalmia associated transcription factor) is essential for melanocyte development and acts as a master regulator of this cell type. Mice carrying loss-of-function mutations in Mitf lack melanocytes altogether and in humans, MITF mutatio...
Differential intracellular pH plays an important role in organelle function and intracellular transport. The intracellular distribution of cancer drugs is also influenced by pH gradients. A wide range of biological activities has been described for the lichen compund usnic acid (UA) e.g., anti-inflammatory, anti-viral and anti-bacterial activity. U...
Mammalian Target of Rapamycin Complex 1 (mTORC1) is activated by growth factor-regulated phosphoinositide 3-kinase (PI3K)/Akt/Rheb signalling and extracellular amino acids (AAs) to promote growth and proliferation. These AAs induce translocation of mTOR to late endosomes and lysosomes (LELs), subsequent activation via mechanisms involving the prese...
PAT-GFP insertions are expressed at different levels in vivo. Different UAS-PAT-GFP insertion lines and the two Gene Search insertion lines [72]
CG1139GS10666 and pathGS13857, were expressed using the Lsp2-GAL4 driver [50], [55], which produces detectable fusion protein in the fat body with all PAT-GFP lines tested (e.g., Figure 6). Levels of CG113...
Subcloning, production of transgenic fly lines, measurement of mRNA levels in
Drosophila
fat bodies, fat body immunostaining.
(DOC)
Expression pattern of endosomal markers in the Drosophila larval fat body. (A–D) Figure shows expression of the FYVE-GFP (early endosomal; A, B) and HRP-Lamp1 (late endosomal; C, D) markers in the larval fat body. In the presence (B, D) and absence (A, C) of Rheb, FYVE-GFP (green) is largely confined to a perinuclear region (arrows), while HRP-Lamp...
The phosphoinositide3-kinase (PI3K)/Akt and downstream mammalian target of rapamycin complex 1 (mTORC1) signalling cascades promote normal growth and are frequently hyperactivated in tumour cells. mTORC1 is also regulated by local nutrients, particularly amino acids, but the mechanisms involved are poorly understood. Unexpectedly, members of the pr...
mTOR (mammalian target of rapamycin) plays a key role in determining how growth factor, nutrient and oxygen levels modulate intracellular events critical for the viability and growth of the cell. This is reflected in the impact of aberrant mTOR signalling on a number of major human diseases and has helped to drive research to understand how TOR (ta...
The IIS (insulin/IGF (insulin-like growth factor) signalling) cascade has an important role in regulating normal development and physiology, as evidenced by its effects in a host of major human diseases including cancer, Type 2 diabetes and neurodegeneration. Recently, it has become clear that multiple types of local nutrient-sensing mechanisms hav...
Maedi-visna virus (MVV) is a lentivirus of sheep causing chronic inflammatory disease of the lungs (maedi) and the nervous
system (visna). We have previously shown that a duplicated sequence in the long terminal repeat (LTR) of MVV is a determinant
of cell tropism. Here, we demonstrate that deletion of a CAAAT sequence from either one of the repeat...