A5045014908- Mitochondrial Function and Pathology
- Adipose Tissue and Metabolism
- Lysosomal Storage Disorders Research
- ATP Synthase and ATPases Research
- Metabolism and Genetic Disorders
- Carbohydrate Chemistry and Synthesis
- Parkinson's Disease Mechanisms and Treatments
- Metabolomics and Mass Spectrometry Studies
- Physiological and biochemical adaptations
- Genetic Neurodegenerative Diseases
- Trypanosoma species research and implications
- Glycogen Storage Diseases and Myoclonus
- Pluripotent Stem Cells Research
- RNA Research and Splicing
- Zebrafish Biomedical Research Applications
- Folate and B Vitamins Research
- interferon and immune responses
- Neuroscience and Neuropharmacology Research
- thermodynamics and calorimetric analyses
- Forensic Entomology and Diptera Studies
- biodegradable polymer synthesis and properties
- Autophagy in Disease and Therapy
- Cellular transport and secretion
- Research in Social Sciences
- Pancreatitis Pathology and Treatment
Tampere University
2023-2025
University of Helsinki
2016-2024
La Trobe University
2023
Max Planck Institute for Biology of Ageing
2010-2013
Karolinska Institutet
2007-2012
Hacettepe University
1999-2002
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2002
National Institutes of Health
2002
Mitochondrial dysfunction is implicated in the pathophysiology of Parkinson's disease (PD), a common age-associated neurodegenerative characterized by intraneuronal inclusions (Lewy bodies) and progressive degeneration nigrostriatal dopamine (DA) system. It has recently been demonstrated that midbrain DA neurons PD patients elderly humans contain high levels somatic mtDNA mutations, which may impair respiratory chain function. However, clinical studies have not established whether deficiency...
At present, there are few means to track symptomatic stages of CNS aging. Thus, although metabolic changes implicated in mtDNA mutation-driven aging, the manifestations remain unclear. Here, we used normally aging and prematurely mutator mice establish a molecular link between mitochondrial dysfunction abnormal metabolism process. Using proton magnetic resonance spectroscopy HPLC, found that brain lactate levels were increased twofold both during To correlate striking increase with tissue...
Mitochondrial dysfunction is implicated in aging and degenerative disorders such as Parkinson's disease (PD). Continuous fission fusion of mitochondria shapes their morphology essential to maintain oxidative phosphorylation. Loss-of-function mutations PTEN-induced kinase1 (PINK1) or Parkin cause a recessive form PD have been linked altered regulation mitochondrial dynamics. More specifically, the E3 ubiquitin ligase has shown directly regulate levels mitofusin 1 (Mfn1) Mfn2, two homologous...
Abstract Mitochondria are critical modulators of antiviral tolerance through the release mitochondrial RNA and DNA (mtDNA mtRNA) fragments into cytoplasm after infection, activating virus sensors type-I interferon (IFN-I) response 1–4 . The relevance these mechanisms for diseases remains understudied. Here we investigated recessive ataxia syndrome (MIRAS), which is caused by a common European founder mutation in polymerase gamma ( POLG1 ) 5 Patients homozygous MIRAS variant p.W748S show...
Abstract Mitochondrial dysfunction manifests as different neurological diseases, but the mechanisms underlying clinical variability remain poorly understood. To clarify whether brain cells have differential sensitivity to mitochondrial dysfunction, we induced DNA (mtDNA) depletion in either neurons or astrocytes of mice, by inactivating Twinkle (TwKO), replicative mtDNA helicase. Here show that astrocytes, most abundant cerebral cell type, are chronically activated upon loss, leading...
Based on studies with a fluorescent reporter dye, Mito Thermo Yellow (MTY), and the genetically encoded gTEMP ratiometric temperature indicator targeted to mitochondria, of active mitochondria in four mammalian one insect cell line was estimated be up 15°C above that external environment which cells were exposed. High mitochondrial maintained face variety metabolic stresses, including substrate starvation or modification, decreased ATP demand due inhibition cytosolic protein synthesis,...
Glycogen storage disease type 1a is caused by a deficiency in glucose-6-phosphatase (G6Pase), nine-helical endoplasmic reticulum transmembrane protein required for maintenance of glucose homeostasis. To date, 75 G6Pase mutations have been identified, including 48 resulting single-amino acid substitutions. However, only 19 missense functionally characterized. Here, we report the results structure and function studies ΔF327 codon deletion mutation, grouped as active site, helical, nonhelical...
Mitochondria are central organelles to cellular metabolism. Their function relies largely on nuclear-encoded proteins that must be imported from the cytosol, and thus protein import pathways important for maintenance of mitochondrial proteostasis. Mitochondrial HSP70 (mtHsp70) is a key component in facilitating translocation through inner membrane into matrix. Its folding cycle regulated by nucleotide-exchange factor GrpE, which triggers release folded ATP rebinding. Vertebrates have two...
Based on studies with a fluorescent reporter dye, Mito Thermo Yellow (MTY), and the genetically encoded gTEMP ratiometric temperature indicator targeted to mitochondria, of active mitochondria in four mammalian one insect cell line was estimated be up 15°C above that external environment which cells were exposed. High mitochondrial maintained face variety metabolic stresses, including substrate starvation or modification, decreased ATP demand due inhibition cytosolic protein synthesis,...
Heteroplasmic mitochondrial DNA (mtDNA) mutations (mutations present only in a subset of cellular mtDNA copies) arise de novo during the normal ageing process or may be maternally inherited pedigrees with disease syndromes. A pathogenic mutation causes respiratory chain deficiency if fraction mutated exceeds certain threshold level. These often undergo apparently random mitotic segregation and levels can vary considerably between cells same tissue. In human ageing, somatic leads to mosaic...
The temperate climate adapted brown hare (Lepus europaeus) and the cold-adapted mountain timidus) are evolutionarily closely related interfertile. Still, their cultured skin fibroblasts show clear differences in expression of genes to basic cellular metabolism. To study this further, we utilized targeted metabolomics analysis, metabolite tracing, high-resolution respirometry, identified significant metabolic pathways associated with adaptive thermogenesis, including a higher rate glycerol...
Mucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disorder caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS; EC 3.1.6.4). The leads to accumulation undegraded glycosaminoglycans, keratan sulfate and chondroitin-6-sulfate. Mutation screening GALNS gene was performed SSCP direct sequence analyses using genomic DNA samples from 10 Morquio A patients. By nonradioactive screening, 6 different mutations 2 polymorphisms were identified in severely affected MPS...
Sanfilippo syndrome (mucopolysaccharidosis type III, MPS III) is a progressive disorder in which patients are characterized by severe central nervous system degeneration together with mild somatic disease. III results from deficiency one of the four enzymes involved degradation heparan sulfate, sulfamidase (SGSH) being deficient IIIA and a-N-acetylglucosaminidase (NAGLU) IIIB. Mutation screening using SSCP/heteroduplex analysis on genomic DNA fragments was performed five Turkish eight IIIB...
CRISPR/Cas9 driven mutagenesis in zygotes is a popular tool for introducing targeted mutations model organisms. Compared to mouse, zebrafish relatively inefficient and results somatic mosaicism most likely due short single-cell stage of about 40 min. Here we explored two options improve zebrafish-extending the defining conditions carrying out oocytes prior vitro fertilization. Previous work has shown that ovarian fluid from North American salmon species (coho chinook salmon) prolong oocyte...
Based on studies with a fluorescent reporter dye, Mito Thermo Yellow, and the genetically encoded gTEMP ratiometric temperature indicator targeted to mitochondria, of active mitochondria in four mammalian one insect cell-line was estimated be up 15 °C above that external environment which cells were exposed. High mitochondrial maintained face variety metabolic stresses, including substrate starvation or modification, decreased ATP demand due inhibition cytosolic protein synthesis, adenine...
Based on studies with a fluorescent reporter dye, Mito Thermo Yellow, and the genetically encoded gTEMP ratiometric temperature indicator targeted to mitochondria, of active mitochondria in four mammalian one insect cell-line was estimated be up 15 °C above that external environment which cells were exposed. High mitochondrial maintained face variety metabolic stresses, including substrate starvation or modification, decreased ATP demand due inhibition cytosolic protein synthesis, adenine...