共查询到20条相似文献,搜索用时 15 毫秒
1.
Wiuf C 《Genetics》2001,159(2):749-756
The possibility of recombination in human mitochondrial DNA (mtDNA) has been hotly debated over the last few years. In this study, a general model of recombination in circular molecules is developed and applied to a recently published African sample (n = 21) of complete mtDNA sequences. It is shown that the power of correlation measures to detect recombination in circular molecules can be vanishingly small and that the data are consistent with the given model and no recombination only if the overall heterogeneity in mutation rate is <0.09. 相似文献
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Emmanouilidou E Elenis D Papasilekas T Stranjalis G Gerozissis K Ioannou PC Vekrellis K 《PloS one》2011,6(7):e22225
Genetic, biochemical, and animal model studies strongly suggest a central role for α-synuclein in the pathogenesis of Parkinson's disease. α-synuclein lacks a signal peptide sequence and has thus been considered a cytosolic protein. Recent data has suggested that the protein may be released from cells via a non-classical secretory pathway and may therefore exert paracrine effects in the extracellular environment. However, proof that α-synuclein is actually secreted into the brain extracellular space in vivo has not been obtained. We developed a novel highly sensitive ELISA in conjugation with an in vivo microdialysis technique to measure α-synuclein in brain interstitial fluid. We show for the first time that α-synuclein is readily detected in the interstitial fluid of both α-synuclein transgenic mice and human patients with traumatic brain injury. Our data suggest that α-synuclein is physiologically secreted by neurons in vivo. This interstitial fluid pool of the protein may have a role in the propagation of synuclein pathology and progression of Parkinson's disease. 相似文献
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Rose G Passarino G Franceschi C De Benedictis G 《The international journal of biochemistry & cell biology》2002,34(11):1449-1460
The impressive performance of the research in mitochondrial genetics and human aging in the last decade outlines a new scenery in which the inherited variation of the mitochondrial genome (mtDNA) may play a role in rate and quality of aging. This variation in humans was initially looked at as nearly neutral, and useful just for the reconstruction of human population history. However, recent data suggest that different mtDNA molecules are qualitatively different from each other. The aim of this paper is to discuss current ideas on the relationships among mitochondrial function, mtDNA inherited variation, and aging. The main processes where the mitochondrion is involved and the importance these processes have on aging and death of individuals will be described. A possible connection between programmed death phenomena (mitoptosis, apoptosis, phenoptosis) and rate and quality of aging will be discussed. Finally, the possible role played in these processes by the mtDNA germline variation will be explored. 相似文献
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Structure and function of the N‐terminal domain of the human mitochondrial calcium uniporter
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Youngjin Lee Choon Kee Min Tae Gyun Kim Hong Ki Song Yunki Lim Dongwook Kim Kahee Shin Moonkyung Kang Jung Youn Kang Hyung‐Seop Youn Jung‐Gyu Lee Jun Yop An Kyoung Ryoung Park Jia Jia Lim Ji Hun Kim Ji Hye Kim Zee Yong Park Yeon‐Soo Kim Jimin Wang Do Han Kim Soo Hyun Eom 《EMBO reports》2015,16(10):1318-1333
The mitochondrial calcium uniporter (MCU) is responsible for mitochondrial calcium uptake and homeostasis. It is also a target for the regulation of cellular anti‐/pro‐apoptosis and necrosis by several oncogenes and tumour suppressors. Herein, we report the crystal structure of the MCU N‐terminal domain (NTD) at a resolution of 1.50 Å in a novel fold and the S92A MCU mutant at 2.75 Å resolution; the residue S92 is a predicted CaMKII phosphorylation site. The assembly of the mitochondrial calcium uniporter complex (uniplex) and the interaction with the MCU regulators such as the mitochondrial calcium uptake‐1 and mitochondrial calcium uptake‐2 proteins (MICU1 and MICU2) are not affected by the deletion of MCU NTD. However, the expression of the S92A mutant or a NTD deletion mutant failed to restore mitochondrial Ca2+ uptake in a stable MCU knockdown HeLa cell line and exerted dominant‐negative effects in the wild‐type MCU‐expressing cell line. These results suggest that the NTD of MCU is essential for the modulation of MCU function, although it does not affect the uniplex formation. 相似文献
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Pantetheinase is an amidohydrolase involved in the dissimilative pathway of CoA, allowing the turnover of the pantothenate moiety. We have determined the N-terminal sequence as well as the sequences of a number of tryptic and chymotryptic peptides of the protein isolated from pig kidney. These sequence stretches were used as probes to search in the SwissProt database and significant similarities were found with a GPI-anchored protein (mouse vanin-1, with a suggested role in lymphocyte migration), with two putative proteins encoded by human cDNAs (VNN1 and VNN2) and with human biotinidase. On the basis of sequence similarity, we propose that vanin-1 and VNN1 should be identified as pantetheinase. 相似文献
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Five female transgenic mice were produced by microinjection using a construct made up of a 7.3-kb-5′ flanking region and a
2.0-kb coding region of human α-lactalbumin, as well as a 227-bp 3′-flanking region from bovine growth hormone gene. A founder
female expressed human α-lactalbumin as much as 0.3 g per liter of its milk, approximately a 3-fold increase in the total
α-lactalbumin concentration of the transgenic mouse milk. Compared with the normal mice, the expression profile of thehα-Lac transgene in the transgenics is different during the lactation, showing low level in the first 3 days and becoming increased
from day 4, then gradually reaching and stabilizing at the highest level from day 13. In addition, the milk yielding volume
in the transgenics tended to be higher than in normal mice, suggesting higher concentrations of α-lactalbumin might boost
more milk output. 相似文献
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LIU Siguo WEI Yingyun HU Guofa GAO Hong LIU Sijin LAO Weide 《中国科学:生命科学英文版》2004,47(3):197-202
Five female transgenic mice were produced by microinjection using a construct made up of a 7.3-kb-5′ flanking region and a 2.0-kb coding region of human α-lactalbumin, as well as a 227-bp 3′-flanking region from bovine growth hormone gene. A founder female expressed human α-lactalbumin as much as 0.3 g per liter of its milk, approximately a 3-fold increase in the total α-lactalbumin concentration of the transgenic mouse milk. Compared with the normal mice, the expression profile of the hα-Lac transgene in the transgenics is different during the lactation, showing low level in the first 3 days and becoming increased from day 4, then gradually reaching and stabilizing at the highest level from day 13. In addition, the milk yielding volume in the transgenics tended to be higher than in normal mice, suggesting higher concentrations of α-lactalbumin might boost more milk output. 相似文献
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The purpose of this study was to determine mitochondrial changes in fast muscles from interleukin-15 receptor alpha knockout (IL-15RαKO) mice. We tested the hypothesis that fast muscles from IL-15RαKO mice would have a greater mitochondrial density and altered internal structure compared to muscles from control mice. In fast muscles from IL-15RαKO mice, mitochondrial density was 48% greater with a corresponding increase in mitochondrial DNA content. Although there were no differences in the relative size of isolated mitochondria, internal complexity was lower in mitochondria from IL-15RαKO mice. These data support an increase in mitochondrial biogenesis and provide direct evidence for a greater density and altered internal structure of mitochondria in EDL muscles deficient in IL-15Rα. 相似文献
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LIU Siguo WEI Yingyun HU Guofa GAO Hong LIU Sijin & LAO Weide Institute of Genetics Developmental Biology Chinese Academy of Sciences Beijing China 《中国科学:生命科学英文版》2004,(3)
a-lactalbumin(a-Lac),amajorwheyprotein,isacalciummetalloprotein,thathasbeenfoundinallmilksstudiedsofar.ItinteractswithUDP-galactosyl-transferasetoformthelactosesynthetaseandthusmightbeakeyproteinforlactogenesis.Lactosesyn-thetaseispostulatedtobetherate-limitingenzymeforlactosebiosynthesis.Theincreaseda-Lacactivitycanproducesufficientlactosesynthetaseforthesynthesisoflactose,andinmilkyieldbydrawingwaterintomilk,sincelactoseisanosmoreactivemolecule.Transgenicswineoverexpressingbovinea-lactalbu… 相似文献
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Female eutherians silence one of their X chromosomes to accomplish an equal dose of X-linked gene expression compared with
males. The mouse is the most widely used animal model in XCI research and has proven to be of great significance for understanding
the complex mechanism of X-linked dosage compensation. Although the basic principles of XCI are similar in mouse and humans,
differences exist in the timing of XCI initiation, the genetic elements involved in XCI regulation and the form of XCI in
specific tissues. Therefore, the mouse has its limitations as a model to understand early human XCI and analysis of human
tissues is required. In this review, we describe these differences with respect to initiation of XCI in human and mouse preimplantation
embryos, the extra-embryonic tissues and the in vitro model of the epiblast: the embryonic stem cells. 相似文献
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M. Di Re H. Sembongi J. He A. Reyes T. Yasukawa P. Martinsson L. J. Bailey S. Goffart J. D. Boyd-Kirkup T. S. Wong A. R. Fersht J. N. Spelbrink I. J. Holt 《Nucleic acids research》2009,37(17):5701-5713
The accessory subunit of mitochondrial DNA polymerase γ, POLGβ, functions as a processivity factor in vitro. Here we show POLGβ has additional roles in mitochondrial DNA metabolism. Mitochondrial DNA is arranged in nucleoprotein complexes, or nucleoids, which often contain multiple copies of the mitochondrial genome. Gene-silencing of POLGβ increased nucleoid numbers, whereas over-expression of POLGβ reduced the number and increased the size of mitochondrial nucleoids. Both increased and decreased expression of POLGβ altered nucleoid structure and precipitated a marked decrease in 7S DNA molecules, which form short displacement-loops on mitochondrial DNA. Recombinant POLGβ preferentially bound to plasmids with a short displacement-loop, in contrast to POLGα. These findings support the view that the mitochondrial D-loop acts as a protein recruitment centre, and suggest POLGβ is a key factor in the organization of mitochondrial DNA in multigenomic nucleoprotein complexes. 相似文献
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Levy Shawn E. Waymire Katrina G. Kim Yoon L. MacGregor Grant R. Wallace Douglas C. 《Transgenic research》1999,8(2):137-145
The mitochondrial DNA (mtDNA) chloramphenicol (CAP)resistance (CAPR) mutation has been introduced into the tissues of adult mice via female embryonic stem (ES) cells. The endogenous CAPsensitive (CAPS) mtDNAs were eliminated by treatment of the ES cells with the lipophilic dye Rhodamine6G (R6G). The ES cells were then fused to enucleated cell cytoplasts prepared from the CAPR mouse cell line 5011. This procedure converted the ES cell mtDNA from 100% wildtype to 100% mutant. The CAPR ES cells were then injected into blastocysts and viable chimeric mice were isolated. Molecular testing for the CAPR mutant mtDNAs revealed that the percentage of mutant mtDNAs varied from zero to approximately 50% in the tissues analyzed. The highest percentage of mutant mtDNA was found in the kidney in three of the chimeric animals tested. These data suggest that, with improved efficiency, it may be possible to transmit exogenous mtDNA mutants through the mouse germline. 相似文献
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Disease-related versus polymorphic mutations in human mitochondrial tRNAs: Where is the difference?
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A number of point mutations in human mitochondrial (mt) tRNA genes are correlated with a variety of neuromuscular and other severe disorders including encephalopathies, myopathies, cardiopathies and diabetes. The complexity of the genotype/phenotype relationships, the diversity of possible molecular impacts of the different mutations at the tRNA structure/function levels, and the exponential discovery of new mutations call for the search for unifying features. Here, the basic features (at the levels of primary and secondary structure) of 68 ‘pathogenic’ mutations are compared with those of 64 ‘polymorphic’ neutral mutations, revealing that these standard parameters for mutant analysis are not sufficient to predict the pathogenicity of mt tRNA mutations. Thus, case by case molecular investigation remains the only means of assessing the growing family of pathogenic mutations in mt tRNAs. New lines of research are suggested. 相似文献
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Vincent Ollendorff Pierre Szepetowski Marie-Genevière Mattei Patrick Gaudray Daniel Birnbaum 《Mammalian genome》1992,2(3):195-200
Alterations in the chromosomal region 11q13–11q14 are involved in several pathologies in which most of the key genes remain to be identified. In an effort to isolate as many candidates as possible, we are cloning genes from this region. We report here the mapping for a new sequence from 11q13.5–11q14. This sequence, designated D11S833E, putatively encodes a new gene, provisionally named GARP. We cloned its homologous sequence in the mouse and located it on Chromosome (Chr) 7, region F. The human and mouse genes belong to a conserved group of synteny. This, together with the similar conservation of the FGF and TYR genes, indicates that the human 11q13–q14 and mouse 7E-7F regions share homology. 相似文献