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91.
92.
Human mitochondrial tRNAs in health and disease 总被引:6,自引:0,他引:6
Florentz C Sohm B Tryoen-Tóth P Pütz J Sissler M 《Cellular and molecular life sciences : CMLS》2003,60(7):1356-1375
The human mitochondrial genome encodes 13 proteins, all subunits of the respiratory chain
complexes and thus involved in energy metabolism. These genes are translated by 22 transfer RNAs
(tRNAs), also encoded by the mitochondrial genome, which form the minimal set required for reading
all codons. Human mitochondrial tRNAs gained interest with the rapid discovery of correlations
between point mutations in their genes and various neuromuscular and neurodegenerative disorders.
In this review, emerging fundamental knowledge on the structure/function relationships of these
particular tRNAs and an overview of the large variety of mechanisms within translation, affected by
mutations, are summarized. Also, initial results on wide-ranging molecular consequences of mutations
outside the frame of mitochondrial translation are highlighted. While knowledge of mitochondrial
tRNAs in both health and disease increases, deciphering the intricate network of events leading
different genotypes to the variety of phenotypes requires further investigation using adapted
model systems.Received 3 December 2002; received after revision 14 January 2003; accepted 27 January 2003 相似文献
93.
Ectopic beta-chain of ATP synthase is an apolipoprotein A-I receptor in hepatic HDL endocytosis 总被引:12,自引:0,他引:12
Martinez LO Jacquet S Esteve JP Rolland C Cabezón E Champagne E Pineau T Georgeaud V Walker JE Tercé F Collet X Perret B Barbaras R 《Nature》2003,421(6918):75-79
The effect of high-density lipoprotein (HDL) in protecting against atherosclerosis is usually attributed to its role in 'reverse cholesterol transport'. In this process, HDL particles mediate the efflux and the transport of cholesterol from peripheral cells to the liver for further metabolism and bile excretion. Thus, cell-surface receptors for HDL on hepatocytes are chief partners in the regulation of cholesterol homeostasis. A high-affinity HDL receptor for apolipoprotein A-I (apoA-I) was previously identified on the surface of hepatocytes. Here we show that this receptor is identical to the beta-chain of ATP synthase, a principal protein complex of the mitochondrial inner membrane. Different experimental approaches confirm this ectopic localization of components of the ATP synthase complex and the presence of ATP hydrolase activity at the hepatocyte cell surface. Receptor stimulation by apoA-I triggers the endocytosis of holo-HDL particles (protein plus lipid) by a mechanism that depends strictly on the generation of ADP. We confirm this effect on endocytosis in perfused rat liver ex vivo by using a specific inhibitor of ATP synthase. Thus, membrane-bound ATP synthase has a previously unsuspected role in modulating the concentrations of extracellular ADP and is regulated by a principal plasma apolipoprotein. 相似文献
94.
Regulatory defects in liver and intestine implicate abnormal hepcidin and Cybrd1 expression in mouse hemochromatosis 总被引:21,自引:0,他引:21
Muckenthaler M Roy CN Custodio AO Miñana B deGraaf J Montross LK Andrews NC Hentze MW 《Nature genetics》2003,34(1):102-107
Individuals with hereditary hemochromatosis suffer from systemic iron overload due to duodenal hyperabsorption. Most cases arise from a founder mutation in HFE (845G-->A; ref. 2) that results in the amino-acid substitution C282Y and prevents the association of HFE with beta2-microglobulin. Mice homozygous with respect to a null allele of Hfe (Hfe-/-) or homozygous with respect to the orthologous 882G-->A mutation (Hfe(845A/845A)) develop iron overload that recapitulates hereditary hemochromatosis in humans, confirming that hereditary hemochromatosis arises from loss of HFE function. Much work has focused on an exclusive role for the intestine in hereditary hemochromatosis. HFE deficiency in intestinal crypt cells is thought to cause intestinal iron deficiency and greater expression of iron transporters such as SLC11A2 (also called DMT1, DCT1 and NRAMP2) and SLC11A3 (also called IREG1, ferroportin and MTP1; ref. 3). Published data on the expression of these transporters in the duodenum of HFE-deficient mice and humans are contradictory. In this report, we used a custom microarray to assay changes in duodenal and hepatic gene expression in Hfe-deficient mice. We found unexpected alterations in the expression of Slc39a1 (mouse ortholog of SLC11A3) and Cybrd1, which encode key iron transport proteins, and Hamp (hepcidin antimicrobial peptide), a hepatic regulator of iron transport. We propose that inappropriate regulatory cues from the liver underlie greater duodenal iron absorption, possibly involving the ferric reductase Cybrd1. 相似文献
95.
Rapid degradation of a large fraction of newly synthesized proteins by proteasomes 总被引:47,自引:0,他引:47
MHC class I molecules function to present peptides eight to ten residues long to the immune system. These peptides originate primarily from a cytosolic pool of proteins through the actions of proteasomes, and are transported into the endoplasmic reticulum, where they assemble with nascent class I molecules. Most peptides are generated from proteins that are apparently metabolically stable. To explain this, we previously proposed that peptides arise from proteasomal degradation of defective ribosomal products (DRiPs). DRiPs are polypeptides that never attain native structure owing to errors in translation or post-translational processes necessary for proper protein folding. Here we show, first, that DRiPs constitute upwards of 30% of newly synthesized proteins as determined in a variety of cell types; second, that at least some DRiPs represent ubiquitinated proteins; and last, that ubiquitinated DRiPs are formed from human immunodeficiency virus Gag polyprotein, a long-lived viral protein that serves as a source of antigenic peptides. 相似文献
96.
Progress in the field of superconductivity is often linked to the discovery of new classes of materials, with the layered copper oxides being a particularly impressive example. The superconductors known today include a wide spectrum of materials, ranging in complexity from simple elemental metals, to alloys and binary compounds of metals, to multi-component compounds of metals and chalcogens or metalloids, doped fullerenes and organic charge-transfer salts. Here we present a new class of superconductors: insulating organic molecular crystals that are made metallic through charge injection. The first examples are pentacene, tetracene and anthracene, the last having the highest transition temperature, at 4 K. We anticipate that many other organic molecular crystals can also be made superconducting by this method, which will lead to surprising findings in the vast composition space of molecular crystals. 相似文献
97.
Crystal structure of the hereditary haemochromatosis protein HFE complexed with transferrin receptor 总被引:26,自引:0,他引:26
HFE is related to major histocompatibility complex (MHC) class I proteins and is mutated in the iron-overload disease hereditary haemochromatosis. HFE binds to the transferrin receptor (TfR), a receptor by which cells acquire iron-loaded transferrin. The 2.8 A crystal structure of a complex between the extracellular portions of HFE and TfR shows two HFE molecules which grasp each side of a twofold symmetric TfR dimer. On a cell membrane containing both proteins, HFE would 'lie down' parallel to the membrane, such that the HFE helices that delineate the counterpart of the MHC peptide-binding groove make extensive contacts with helices in the TfR dimerization domain. The structures of TfR alone and complexed with HFE differ in their domain arrangement and dimer interfaces, providing a mechanism for communicating binding events between TfR chains. The HFE-TfR complex suggests a binding site for transferrin on TfR and sheds light upon the function of HFE in regulating iron homeostasis. 相似文献
98.
Superconductivity at 52 K in hole-doped C60 总被引:4,自引:0,他引:4
Superconductivity in electron-doped C60 was first observed almost ten years ago. The metallic state and superconductivity result from the transfer of electrons from alkaline or alkaline-earth ions to the C60 molecule, which is known to be a strong electron acceptor. For this reason, it is very difficult to remove electrons from C60--yet one might expect to see superconductivity at higher temperatures in hole-doped than in electron-doped C60, because of the higher density of electronic states in the valence band than in the conduction band. We have used the technique of gate-induced doping in a field-effect transistor configuration to introduce significant densities of holes into C60. We observe superconductivity over an extended range of hole density, with a smoothly varying transition temperature Tc that peaks at 52 K. By comparison with the well established dependence of Tc on the lattice parameter in electron-doped C60, we anticipate that Tc values significantly in excess of 100 K should be achievable in a suitably expanded, hole-doped C60 lattice. 相似文献
99.
Establishing the age at death of individuals is an important step in their identification and can be done with high precision up to adolescence by analysis of dentition, but it is more difficult in adults. Here we show that the amount of radiocarbon present in tooth enamel as a result of nuclear bomb testing during 1955-63 is a remarkably accurate indicator of when a person was born. Age is determined to within 1.6 years, whereas the commonly used morphological evaluation of skeletal remains and tooth wear is sensitive to within 5-10 years in adults. 相似文献
100.
Miklós Rédei Iñaki San Pedro 《Studies in History and Philosophy of Science Part B: Studies in History and Philosophy of Modern Physics》2012,43(2):84-89
We distinguish two sub-types of each of the two causality principles formulated in connection with the Common Cause Principle in Henson (2005) and raise and investigate the problem of logical relations among the resulting four causality principles. Based in part on the analysis of the status of these four principles in algebraic quantum field theory we will argue that the four causal principles are non-equivalent. 相似文献