TY - JOUR A1 - Witt, Barbara A1 - Stiboller, Michael A1 - Raschke, Stefanie A1 - Friese, Sharleen A1 - Ebert, Franziska A1 - Schwerdtle, Tanja T1 - Characterizing effects of excess copper levels in a human astrocytic cell line with focus on oxidative stress markers JF - Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements, GMS N2 - Background: Being an essential trace element, copper is involved in diverse physiological processes. However, excess levels might lead to adverse effects. Disrupted copper homeostasis, particularly in the brain, has been associated with human diseases including the neurodegenerative disorders Wilson and Alzheimer?s disease. In this context, astrocytes play an important role in the regulation of the copper homeostasis in the brain and likely in the prevention against neuronal toxicity, consequently pointing them out as a potential target for the neurotoxicity of copper. Major toxic mechanisms are discussed to be directed against mitochondria probably via oxidative stress. However, the toxic potential and mode of action of copper in astrocytes is poorly understood, so far. Methods: In this study, excess copper levels affecting human astrocytic cell model and their involvement in the neurotoxic mode of action of copper, as well as, effects on the homeostasis of other trace elements (Mn, Fe, Ca and Mg) were investigated. Results: Copper induced substantial cytotoxic effects in the human astrocytic cell line following 48 h incubation (EC30: 250 ?M) and affected mitochondrial function, as observed via reduction of mitochondrial membrane potential and increased ROS production, likely originating from mitochondria. Moreover, cellular GSH metabolism was altered as well. Interestingly, not only cellular copper levels were affected, but also the homeostasis of other elements (Ca, Fe and Mn) were disrupted. Conclusion: One potential toxic mode of action of copper seems to be effects on the mitochondria along with induction of oxidative stress in the human astrocytic cell model. Moreover, excess copper levels seem to interact with the homeostasis of other essential elements such as Ca, Fe and Mn. Disrupted element homeostasis might also contribute to the induction of oxidative stress, likely involved in the onset and progression of neurodegenerative disorders. These insights in the toxic mechanisms will help to develop ideas and approaches for therapeutic strategies against copper-mediated diseases. KW - Copper KW - Astrocytes KW - Toxicity KW - Mitochondria KW - ROS KW - Trace elements Y1 - 2021 U6 - https://doi.org/10.1016/j.jtemb.2021.126711 SN - 1878-3252 VL - 65 PB - Elsevier CY - München ER - TY - JOUR A1 - Ralevski, Alexandra A1 - Apelt, Federico A1 - Olas, Justyna Jadwiga A1 - Müller-Röber, Bernd A1 - Rugarli, Elena I. A1 - Kragler, Friedrich A1 - Horvath, Tamas L. T1 - Plant mitochondrial FMT and its mammalian homolog CLUH controls development and behavior in Arabidopsis and locomotion in mice JF - Cellular and molecular life sciences N2 - Mitochondria in animals are associated with development, as well as physiological and pathological behaviors. Several conserved mitochondrial genes exist between plants and higher eukaryotes. Yet, the similarities in mitochondrial function between plant and animal species is poorly understood. Here, we show that FMT (FRIENDLY MITOCHONDRIA) from Arabidopsis thaliana, a highly conserved homolog of the mammalian CLUH (CLUSTERED MITOCHONDRIA) gene family encoding mitochondrial proteins associated with developmental alterations and adult physiological and pathological behaviors, affects whole plant morphology and development under both stressed and normal growth conditions. FMT was found to regulate mitochondrial morphology and dynamics, germination, and flowering time. It also affects leaf expansion growth, salt stress responses and hyponastic behavior, including changes in speed of hyponastic movements. Strikingly, Cluh(+/-) heterozygous knockout mice also displayed altered locomotive movements, traveling for shorter distances and had slower average and maximum speeds in the open field test. These observations indicate that homologous mitochondrial genes may play similar roles and affect homologous functions in both plants and animals. KW - Arabidopsis thaliana KW - Mitochondria KW - FMT KW - Hyponasty KW - Mice KW - CLUH; KW - Locomotion Y1 - 2022 U6 - https://doi.org/10.1007/s00018-022-04382-3 SN - 1420-682X SN - 1420-9071 VL - 79 IS - 6 PB - Springer International Publishing AG CY - Cham (ZG) ER - TY - JOUR A1 - Paijmans, Johanna L. A. A1 - Barlow, Axel A1 - Henneberger, Kirstin A1 - Fickel, Jörns A1 - Hofreiter, Michael A1 - Foerste, Daniel W. G. T1 - Ancestral mitogenome capture of the Southeast Asian banded linsang JF - PLoS ONE N2 - Utilising a reconstructed ancestral mitochondrial genome of a clade to design hybridisation capture baits can provide the opportunity for recovering mitochondrial sequences from all its descendent and even sister lineages. This approach is useful for taxa with no extant close relatives, as is often the case for rare or extinct species, and is a viable approach for the analysis of historical museum specimens. Asiatic linsangs (genus Prionodon) exemplify this situation, being rare Southeast Asian carnivores for which little molecular data is available. Using ancestral capture we recover partial mitochondrial genome sequences for seven banded linsangs (P. linsang) from historical specimens, representing the first intraspecific genetic dataset for this species. We additionally assemble a high quality mitogenome for the banded linsang using shotgun sequencing for time-calibrated phylogenetic analysis. This reveals a deep divergence between the two Asiatic linsang species (P. linsang, P. pardicolor), with an estimated divergence of ~12 million years (Ma). Although our sample size precludes any robust interpretation of the population structure of the banded linsang, we recover two distinct matrilines with an estimated tMRCA of ~1 Ma. Our results can be used as a basis for further investigation of the Asiatic linsangs, and further demonstrate the utility of ancestral capture for studying divergent taxa without close relatives. KW - Shotgun sequencing KW - Mitochondria KW - Phylogenetics KW - Phylogenetic analysis KW - Paleogenetics KW - Sequence alignment KW - Genomics KW - Museum collections Y1 - 2019 U6 - https://doi.org/10.1371/journal.pone.0234385 SN - 1932-6203 VL - 15 IS - 6 PB - PLOS CY - San Francisco, California, US ER - TY - GEN A1 - Paijmans, Johanna L. A. A1 - Barlow, Axel A1 - Henneberger, Kirstin A1 - Fickel, Jörns A1 - Hofreiter, Michael A1 - Foerste, Daniel W. G. T1 - Ancestral mitogenome capture of the Southeast Asian banded linsang T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Utilising a reconstructed ancestral mitochondrial genome of a clade to design hybridisation capture baits can provide the opportunity for recovering mitochondrial sequences from all its descendent and even sister lineages. This approach is useful for taxa with no extant close relatives, as is often the case for rare or extinct species, and is a viable approach for the analysis of historical museum specimens. Asiatic linsangs (genus Prionodon) exemplify this situation, being rare Southeast Asian carnivores for which little molecular data is available. Using ancestral capture we recover partial mitochondrial genome sequences for seven banded linsangs (P. linsang) from historical specimens, representing the first intraspecific genetic dataset for this species. We additionally assemble a high quality mitogenome for the banded linsang using shotgun sequencing for time-calibrated phylogenetic analysis. This reveals a deep divergence between the two Asiatic linsang species (P. linsang, P. pardicolor), with an estimated divergence of ~12 million years (Ma). Although our sample size precludes any robust interpretation of the population structure of the banded linsang, we recover two distinct matrilines with an estimated tMRCA of ~1 Ma. Our results can be used as a basis for further investigation of the Asiatic linsangs, and further demonstrate the utility of ancestral capture for studying divergent taxa without close relatives. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 972 KW - Shotgun sequencing KW - Mitochondria KW - Phylogenetics KW - Phylogenetic analysis KW - Paleogenetics KW - Sequence alignment KW - Genomics KW - Museum collections Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-474441 SN - 1866-8372 IS - 972 ER - TY - JOUR A1 - Klaus, Susanne A1 - Igual Gil, Carla A1 - Ost, Mario T1 - Regulation of diurnal energy balance by mitokines JF - Cellular and molecular life sciences : CMLS N2 - The mammalian system of energy balance regulation is intrinsically rhythmic with diurnal oscillations of behavioral and metabolic traits according to the 24 h day/night cycle, driven by cellular circadian clocks and synchronized by environmental or internal cues such as metabolites and hormones associated with feeding rhythms. Mitochondria are crucial organelles for cellular energy generation and their biology is largely under the control of the circadian system. Whether mitochondrial status might also feed-back on the circadian system, possibly via mitokines that are induced by mitochondrial stress as endocrine-acting molecules, remains poorly understood. Here, we describe our current understanding of the diurnal regulation of systemic energy balance, with focus on fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15), two well-known endocrine-acting metabolic mediators. FGF21 shows a diurnal oscillation and directly affects the output of the brain master clock. Moreover, recent data demonstrated that mitochondrial stress-induced GDF15 promotes a day-time restricted anorexia and systemic metabolic remodeling as shown in UCP1-transgenic mice, where both FGF21 and GDF15 are induced as myomitokines. In this mouse model of slightly uncoupled skeletal muscle mitochondria GDF15 proved responsible for an increased metabolic flexibility and a number of beneficial metabolic adaptations. However, the molecular mechanisms underlying energy balance regulation by mitokines are just starting to emerge, and more data on diurnal patterns in mouse and man are required. This will open new perspectives into the diurnal nature of mitokines and action both in health and disease. KW - Mitochondria KW - FGF21 KW - GDF15 KW - Circadian rhythm KW - Hormones KW - Nutrition Y1 - 2021 U6 - https://doi.org/10.1007/s00018-020-03748-9 SN - 1420-682X SN - 1420-9071 VL - 78 IS - 7 SP - 3369 EP - 3384 PB - Springer International Publishing AG CY - Cham (ZG) ER - TY - GEN A1 - Hauffe, Robert A1 - Rath, Michaela A1 - Schell, Mareike A1 - Ritter, Katrin A1 - Kappert, Kai A1 - Deubel, Stefanie A1 - Ott, Christiane A1 - Jähnert, Markus A1 - Jonas, Wenke A1 - Schürmann, Annette A1 - Kleinridders, André T1 - HSP60 reduction protects against diet-induced obesity by modulating energy metabolism in adipose tissue T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Objective Insulin regulates mitochondrial function, thereby propagating an efficient metabolism. Conversely, diabetes and insulin resistance are linked to mitochondrial dysfunction with a decreased expression of the mitochondrial chaperone HSP60. The aim of this investigation was to determine the effect of a reduced HSP60 expression on the development of obesity and insulin resistance. Methods Control and heterozygous whole-body HSP60 knockout (Hsp60+/−) mice were fed a high-fat diet (HFD, 60% calories from fat) for 16 weeks and subjected to extensive metabolic phenotyping. To understand the effect of HSP60 on white adipose tissue, microarray analysis of gonadal WAT was performed, ex vivo experiments were performed, and a lentiviral knockdown of HSP60 in 3T3-L1 cells was conducted to gain detailed insights into the effect of reduced HSP60 levels on adipocyte homeostasis. Results Male Hsp60+/− mice exhibited lower body weight with lower fat mass. These mice exhibited improved insulin sensitivity compared to control, as assessed by Matsuda Index and HOMA-IR. Accordingly, insulin levels were significantly reduced in Hsp60+/− mice in a glucose tolerance test. However, Hsp60+/− mice exhibited an altered adipose tissue metabolism with elevated insulin-independent glucose uptake, adipocyte hyperplasia in the presence of mitochondrial dysfunction, altered autophagy, and local insulin resistance. Conclusions We discovered that the reduction of HSP60 in mice predominantly affects adipose tissue homeostasis, leading to beneficial alterations in body weight, body composition, and adipocyte morphology, albeit exhibiting local insulin resistance. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1235 KW - Mitochondria KW - Stress response KW - Obesity KW - Glucose homeostasis KW - Insulin resistance KW - Adipose tissue Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-548002 SN - 1866-8372 SP - 1 EP - 14 PB - Universitätsverlag Potsdam CY - Potsdam ER - TY - JOUR A1 - Hauffe, Robert A1 - Rath, Michaela A1 - Schell, Mareike A1 - Ritter, Katrin A1 - Kappert, Kai A1 - Deubel, Stefanie A1 - Ott, Christiane A1 - Jähnert, Markus A1 - Jonas, Wenke A1 - Schürmann, Annette A1 - Kleinridders, André T1 - HSP60 reduction protects against diet-induced obesity by modulating energy metabolism in adipose tissue JF - Molecular Metabolism N2 - Objective Insulin regulates mitochondrial function, thereby propagating an efficient metabolism. Conversely, diabetes and insulin resistance are linked to mitochondrial dysfunction with a decreased expression of the mitochondrial chaperone HSP60. The aim of this investigation was to determine the effect of a reduced HSP60 expression on the development of obesity and insulin resistance. Methods Control and heterozygous whole-body HSP60 knockout (Hsp60+/−) mice were fed a high-fat diet (HFD, 60% calories from fat) for 16 weeks and subjected to extensive metabolic phenotyping. To understand the effect of HSP60 on white adipose tissue, microarray analysis of gonadal WAT was performed, ex vivo experiments were performed, and a lentiviral knockdown of HSP60 in 3T3-L1 cells was conducted to gain detailed insights into the effect of reduced HSP60 levels on adipocyte homeostasis. Results Male Hsp60+/− mice exhibited lower body weight with lower fat mass. These mice exhibited improved insulin sensitivity compared to control, as assessed by Matsuda Index and HOMA-IR. Accordingly, insulin levels were significantly reduced in Hsp60+/− mice in a glucose tolerance test. However, Hsp60+/− mice exhibited an altered adipose tissue metabolism with elevated insulin-independent glucose uptake, adipocyte hyperplasia in the presence of mitochondrial dysfunction, altered autophagy, and local insulin resistance. Conclusions We discovered that the reduction of HSP60 in mice predominantly affects adipose tissue homeostasis, leading to beneficial alterations in body weight, body composition, and adipocyte morphology, albeit exhibiting local insulin resistance. KW - Mitochondria KW - Stress response KW - Obesity KW - Glucose homeostasis KW - Insulin resistance KW - Adipose tissue Y1 - 2021 U6 - https://doi.org/10.1016/j.molmet.2021.101276 SN - 2212-8778 VL - 53 SP - 1 EP - 14 PB - Elsevier CY - Amsterdam, Niederlande ER - TY - THES A1 - Hauffe, Robert T1 - Investigating metabolic consequences of an HSP60 reduction during diet-induced obesity T1 - Metabolische Folgen einer HSP60 Reduktion während des Diät-induzierten Übergewichts N2 - The mitochondrial chaperone complex HSP60/HSP10 facilitates mitochondrial protein homeostasis by folding more than 300 mitochondrial matrix proteins. It has been shown previously that HSP60 is downregulated in brains of type 2 diabetic (T2D) mice and patients, causing mitochondrial dysfunction and insulin resistance. As HSP60 is also decreased in peripheral tissues in T2D animals, this thesis investigated the effect of overall reduced HSP60 in the development of obesity and associated co-morbidities. To this end, both female and male C57Bl/6N control (i.e. without further alterations in their genome, Ctrl) and heterozygous whole-body Hsp60 knock-out (Hsp60+/-) mice, which exhibit a 50 % reduction of HSP60 in all tissues, were fed a normal chow diet (NCD) or a highfat diet (HFD, 60 % calories from fat) for 16 weeks and were subjected to extensive metabolic phenotyping including indirect calorimetry, NMR spectroscopy, insulin, glucose and pyruvate tolerance tests, vena cava insulin injections, as well as histological and molecular analysis. Interestingly, NCD feeding did not result in any striking phenotype, only a mild increase in energy expenditure in Hsp60+/- mice. Exposing mice to a HFD however revealed an increased body weight due to higher muscle mass in female Hsp60+/- mice, with a simultaneous decrease in energy expenditure. Additionally, these mice displayed decreased fasting glycemia. Opposingly, male Hsp60+/- compared to control mice showed lower body weight gain due to decreased fat mass and an increased energy expenditure, strikingly independent of lean mass. Further, only male Hsp60+/- mice display improved HOMA-IR and Matsuda insulin sensitivity indices. Despite the opposite phenotype in regards to body weight development, Hsp60+/- mice of both sexes show a significantly higher cell number, as well as a reduction in adipocyte size in the subcutaneous and gonadal white adipose tissue (sc/gWAT). Curiously, this adipocyte hyperplasia – usually associated with positive aspects of WAT function – is disconnected from metabolic improvements, as the gWAT of male Hsp60+/- mice shows mitochondrial dysfunction, oxidative stress, and insulin resistance. Transcriptomic analysis of gWAT shows an up regulation of genes involved in macroautophagy. Confirmatory, expression of microtubuleassociated protein 1A/1B light chain 3B (LC3), as a protein marker of autophagy, and direct measurement of lysosomal activity is increased in the gWAT of male Hsp60+/- mice. In summary, this thesis revealed a novel gene-nutrient interaction. The reduction of the crucial chaperone HSP60 did not have large effects in mice fed a NCD, but impacted metabolism during DIO in a sex-specific manner, where, despite opposing body weight and body composition phenotypes, both female and male Hsp60+/- mice show signs of protection from high fat diet-induced systemic insulin resistance. N2 - Der mitochondriale Chaperonkomplex HSP60/10 ist für die korrekte Faltung von über 300 mitochondrialen Matrixproteinen verantwortlich. Es wurde bereits gezeigt, dass HSP60 in Gehirnen von Patienten sowie Mäusen mit Typ 2 Diabetes (T2D) reduziert ist, was zu mitochondrialer Dysfunktion und Insulinresistenz führt. HSP60 ist darüber hinaus auch in peripheren Organen von T2D Mäusen reduziert. Die hier vorliegende Arbeit hat daher den Einfluss einer generellen Reduktion von HSP60 auf die Entwicklung von Übergewicht und die damit assoziierten Komorbiditäten untersucht. Hierfür wurden weibliche und männliche C57Bl/6N Kontroll Mäuse (d.h. ohne wietere Veränderung ihres Genoms, Ctrl), sowie C57Bl/6N Mäuse mit einer heterozygoten Deletion von HSP60 (Hsp60+/-) genutzt. Die Hsp60+/- Maus zeigt eine 50 % Reduktion von HSP60 in allen Geweben. Allen Tieren wurde in der Folge entweder eine normale Haltungsdiät (NCD) oder eine 60 % Hochfettdiät (HFD) gefüttert und einer intensiven metabolischen Charakterisierung unterzogen. Dies beinhaltete indirekte Kalorimetrie, NMR Spektroskopie, Insulin, Glukose und Pyruvat Toleranztests, direkte vena cava Insulinapplikation, sowie eingehende histologische und molekulare Untersuchungen. Interessanterweise zeigte die Fütterung mit der NCD keine stark ausgeprägten Phänotypen, lediglich ein leichter Anstieg im Energieverbrauch war zu beobachten. Die Fütterung mit der HFD dagegen führte auf Grund von größerer Muskelmasse zu einem erhöhten Körpergewicht in weiblichen Hsp60+/- Mäusen, was mit gleichzeitig verringertem Energieverbrauch einherging. Zusätzlich war bei diesen Mäusen der gefastete Bluzuckerspiegel verringert. Im Gegensatz dazu zeigten männliche Hsp60+/- Mäuse ein verringertes Körpergewicht, bedingt durch eine geringere Fettmasse sowie erhöhtem Energieverbrauch. Darüber hinaus war bei männlichen Hsp60+/- Mäusen eine Verbesserung der Insulin Sensitivitätsindizes HOMA-IR und Matsuda Index zu verzeichnen. Trotz dieses gegenteiligen Phänotyps zeigten beide Geschlechter eine erhöhte Zellzahl, sowie eine verringerte Zellgröße der Adipozyten im subkutanen und gonadalen weißen Fettgewebe (sc/gWAT (engl: white adipose tissue)). Überraschenderweise ist diese Adipozytenhyperplasie – normalerweise assoziiert mit verbesserter Fettgewebsfunktion – losgelöst von verbesserter WAT Funktion, da das gWAT männlicher Hsp60+/- Mäuse mitochondriale Dysfunktion, oxidativen Stress und Insulinresistenz zeigt. Eine folgende Transkriptomanalyse gab Hinweise auf eine Induktion der Makroautophagie. Bestätigend hierfür ist im gWAT der heterozygoten Mäuse die Expression des Autophagie Markers microtubule-associated protein 1A/1B light chain 3B (LC3), sowie die direkt gemessene lysosomale Aktivität erhöht. Zusammenfassend konnte in dieser Arbeit eine neuartige Gen-Nährstoff Interaktion gezeigt werden. So zeigte die Reduktion des wichtigen Chaperons HSP60 unter NCD Fütterung nur schwache Effekte, während unter Hochfettdiätfütterung der Stoffwechsel geschlechtsspezifisch beinflusst wurde. Obwohl die beiden Geschlechter der Hsp60+/- Mäuse gegenteilige Phänotypen im Bezug auf Körpergewicht und Körperzusammensetzung aufwiesen, zeigen beide Anzeichen eines Schutzes vor Hochfettdiät-induzierter Insulinresistenz. KW - Obesity KW - Adipose tissue KW - Insulin resistance KW - Mitochondria KW - Fettgewebe KW - Insulinresistenz KW - Mitochondrien KW - Adipositas Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-509294 ER - TY - GEN A1 - Gurke, Marie A1 - Vidal-Gorosquieta, Amalia A1 - Pajimans, Johanna L. A. A1 - Wȩcek, Karolina A1 - Barlow, Axel A1 - González-Fortes, Gloria M. A1 - Hartmann, Stefanie A1 - Grandal-d’Anglade, Aurora A1 - Hofreiter, Michael T1 - Insight into the introduction of domestic cattle and the process of Neolithization to the Spanish region Galicia by genetic evidence T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Domestic cattle were brought to Spain by early settlers and agricultural societies. Due to missing Neolithic sites in the Spanish region of Galicia, very little is known about this process in this region. We sampled 18 cattle subfossils from different ages and different mountain caves in Galicia, of which 11 were subject to sequencing of the mitochondrial genome and phylogenetic analysis, to provide insight into the introduction of cattle to this region. We detected high similarity between samples from different time periods and were able to compare the time frame of the first domesticated cattle in Galicia to data from the connecting region of Cantabria to show a plausible connection between the Neolithization of these two regions. Our data shows a close relationship of the early domesticated cattle of Galicia and modern cow breeds and gives a general insight into cattle phylogeny. We conclude that settlers migrated to this region of Spain from Europe and introduced common European breeds to Galicia. KW - Haplogroups KW - Mitochondria KW - Cattle KW - Genomics KW - Domestic animals KW - Livestock KW - Single nucleotide polymorphisms KW - Neolithic period Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-520875 SN - 1866-8372 IS - 4 ER - TY - JOUR A1 - Gurke, Marie A1 - Vidal-Gorosquieta, Amalia A1 - Pajimans, Johanna L. A. A1 - Wȩcek, Karolina A1 - Barlow, Axel A1 - González-Fortes, Gloria M. A1 - Hartmann, Stefanie A1 - Grandal-d’Anglade, Aurora A1 - Hofreiter, Michael T1 - Insight into the introduction of domestic cattle and the process of Neolithization to the Spanish region Galicia by genetic evidence JF - PLoS ONE N2 - Domestic cattle were brought to Spain by early settlers and agricultural societies. Due to missing Neolithic sites in the Spanish region of Galicia, very little is known about this process in this region. We sampled 18 cattle subfossils from different ages and different mountain caves in Galicia, of which 11 were subject to sequencing of the mitochondrial genome and phylogenetic analysis, to provide insight into the introduction of cattle to this region. We detected high similarity between samples from different time periods and were able to compare the time frame of the first domesticated cattle in Galicia to data from the connecting region of Cantabria to show a plausible connection between the Neolithization of these two regions. Our data shows a close relationship of the early domesticated cattle of Galicia and modern cow breeds and gives a general insight into cattle phylogeny. We conclude that settlers migrated to this region of Spain from Europe and introduced common European breeds to Galicia. KW - Haplogroups KW - Mitochondria KW - Cattle KW - Genomics KW - Domestic animals KW - Livestock KW - Single nucleotide polymorphisms KW - Neolithic period Y1 - 2020 U6 - https://doi.org/10.1371/journal.pone.0249537 SN - 1932-6203 VL - 16 IS - 4 PB - Public Library of Science CY - San Francisco ER - TY - JOUR A1 - Grahn, R. A. A1 - Kurushima, J. D. A1 - Billings, N. C. A1 - Grahn, J. C. A1 - Halverson, J. L. A1 - Hammer, E. A1 - Ho, C. K. A1 - Kun, T. J. A1 - Levy, J. K. A1 - Lipinski, M. J. A1 - Mwenda, J. M. A1 - Ozpinar, H. A1 - Schuster, R. K. A1 - Shoorijeh, S. J. A1 - Tarditi, C. R. A1 - Waly, N. E. A1 - Wictum, E. J. A1 - Lyons, L. A. T1 - Feline non-repetitive mitochondrial DNA control region database for forensic evidence JF - Forensic science international : an international journal dedicated to the applications of genetics in the administration of justice ; Genetics N2 - The domestic cat is the one of the most popular pets throughout the world. A by-product of owning, interacting with, or being in a household with a cat is the transfer of shed fur to clothing or personal objects. As trace evidence, transferred cat fur is a relatively untapped resource for forensic scientists. Both phenotypic and genotypic characteristics can be obtained from cat fur, but databases for neither aspect exist. Because cats incessantly groom, cat fur may have nucleated cells, not only in the hair bulb, but also as epithelial cells on the hair shaft deposited during the grooming process, thereby generally providing material for DNA profiling. To effectively exploit cat hair as a resource, representative databases must be established. The current study evaluates 402 bp of the mtDNA control region (CR) from 1394 cats, including cats from 25 distinct worldwide populations and 26 breeds. Eighty-three percent of the cats are represented by 12 major mitotypes. An additional 8.0% are clearly derived from the major mitotypes. Unique sequences are found in 7.5% of the cats. The overall genetic diversity for this data set is 0.8813 +/- 0.0046 with a random match probability of 11.8%. This region of the cat mtDNA has discriminatory power suitable for forensic application worldwide. KW - Forensic science KW - Domestic cat KW - mtDNA KW - Mitochondria KW - d-Loop KW - Control region Y1 - 2011 U6 - https://doi.org/10.1016/j.fsigen.2010.01.013 SN - 1872-4973 VL - 5 IS - 1 SP - 33 EP - 42 PB - Elsevier CY - Clare ER - TY - JOUR A1 - Fraesdorf, Benjamin A1 - Radon, Christin A1 - Leimkühler, Silke T1 - Characterization and interaction studies of two isoforms of the dual localized 3-mercaptopyruvate sulfurtransferase TUM1 from humans JF - The journal of biological chemistry N2 - Background: Localization and identification of interaction partners of two splice variants of the human 3-mercaptopyruvate sulfurtransferase TUM1. Results: We show that TUM1 interacts with proteins involved in Moco and FeS cluster biosynthesis. Conclusion: Human TUM1 is a dual localized protein in the cytosol and mitochondria with distinct roles in sulfur transfer and interaction partners. Significance: The study contributes to the sulfur transfer pathway for the biosynthesis of sulfur-containing biofactors. The human tRNA thiouridine modification protein (TUM1), also designated as 3-mercaptopyruvate sulfurtransferase (MPST), has been implicated in a wide range of physiological processes in the cell. The roles range from an involvement in thiolation of cytosolic tRNAs to the generation of H2S as signaling molecule both in mitochondria and the cytosol. TUM1 is a member of the sulfurtransferase family and catalyzes the conversion of 3-mercaptopyruvate to pyruvate and protein-bound persulfide. Here, we purified and characterized two novel TUM1 splice variants, designated as TUM1-Iso1 and TUM1-Iso2. The purified proteins showed similar kinetic behavior and comparable pH and temperature dependence. Cellular localization studies, however, showed a different localization pattern between the isoforms. TUM1-Iso1 is exclusively localized in the cytosol, whereas TUM1-Iso2 showed a dual localization both in the cytosol and mitochondria. Interaction studies were performed with the isoforms both in vitro using the purified proteins and in vivo by fluorescence analysis in human cells, using the split-EGFP system. The studies showed that TUM1 interacts with the l-cysteine desulfurase NFS1 and the rhodanese-like protein MOCS3, suggesting a dual function of TUM1 both in sulfur transfer for the biosynthesis of the molybdenum cofactor, and for the thiolation of tRNA. Our studies point to distinct roles of each TUM1 isoform in the sulfur transfer processes in the cell, with different compartmentalization of the two splice variants of TUM1. KW - Fluorescence KW - Mitochondria KW - Molybdenum KW - Sulfur KW - Transfer RNA (tRNA) Y1 - 2014 U6 - https://doi.org/10.1074/jbc.M114.605733 SN - 0021-9258 SN - 1083-351X VL - 289 IS - 50 SP - 34543 EP - 34556 PB - American Society for Biochemistry and Molecular Biology CY - Bethesda ER -