Abstract:
:Mitochondrial genomes (mitochondrial DNA, mtDNA) encode essential oxidative phosphorylation (OXPHOS) components. Because hundreds of mtDNAs exist per cell, a deletion in a single mtDNA has little impact. However, if the deletion genome is enriched, OXPHOS declines, resulting in cellular dysfunction. For example, Kearns-Sayre syndrome is caused by a single heteroplasmic mtDNA deletion. More broadly, mtDNA deletion accumulation has been observed in individual muscle cells and dopaminergic neurons during ageing. It is unclear how mtDNA deletions are tolerated or how they are propagated in somatic cells. One mechanism by which cells respond to OXPHOS dysfunction is by activating the mitochondrial unfolded protein response (UPR(mt)), a transcriptional response mediated by the transcription factor ATFS-1 that promotes the recovery and regeneration of defective mitochondria. Here we investigate the role of ATFS-1 in the maintenance and propagation of a deleterious mtDNA in a heteroplasmic Caenorhabditis elegans strain that stably expresses wild-type mtDNA and mtDNA with a 3.1-kilobase deletion (∆mtDNA) lacking four essential genes. The heteroplasmic strain, which has 60% ∆mtDNA, displays modest mitochondrial dysfunction and constitutive UPR(mt) activation. ATFS-1 impairment reduced the ∆mtDNA nearly tenfold, decreasing the total percentage to 7%. We propose that in the context of mtDNA heteroplasmy, UPR(mt) activation caused by OXPHOS defects propagates or maintains the deleterious mtDNA in an attempt to recover OXPHOS activity by promoting mitochondrial biogenesis and dynamics.
journal_name
Naturejournal_title
Natureauthors
Lin YF,Schulz AM,Pellegrino MW,Lu Y,Shaham S,Haynes CMdoi
10.1038/nature17989subject
Has Abstractpub_date
2016-05-19 00:00:00pages
416-9issue
7603eissn
0028-0836issn
1476-4687pii
nature17989journal_volume
533pub_type
杂志文章相关文献
NATURE文献大全abstract::The 26S proteasome is the chief site of regulatory protein turnover in eukaryotic cells. It comprises one 20S catalytic complex (composed of four stacked rings of seven members) and two axially positioned 19S regulatory complexes (each containing about 18 subunits) that control substrate access to the catalytic chambe...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/416763a
更新日期:2002-04-18 00:00:00
abstract::The evolutionary history of extant hominoids (humans and apes) remains poorly understood. The African fossil record during the crucial time period, the Miocene epoch, largely comprises isolated jaws and teeth, and little is known about ape cranial evolution. Here we report on the, to our knowledge, most complete fossi...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature23456
更新日期:2017-08-09 00:00:00
abstract::The analysis of mutations affecting flower structure has led to the identification of some of the genes that direct flower development. Cloning of these genes has allowed the formulation of molecular models of how floral meristem and organ identity may be specified, and has shown that the distantly related flowering p...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/353031a0
更新日期:1991-09-05 00:00:00
abstract::DNA methylation is an important epigenetic modification that is essential for various developmental processes through regulating gene expression, genomic imprinting, and epigenetic inheritance. Mammalian genomic DNA methylation is established during embryogenesis by de novo DNA methyltransferases, DNMT3A and DNMT3B, a...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature13899
更新日期:2015-01-29 00:00:00
abstract::An essential feature of the bacterial pathogen Salmonella spp. is its ability to enter cells that are normally non-phagocytic, such as those of the intestinal epithelium. The bacterium achieves entry by delivering effector proteins into the host-cell cytosol by means of a specialized protein-secretion system (termed t...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/45829
更新日期:1999-09-16 00:00:00
abstract::The dry valleys of southern Victoria Land in Antarctica contain several closed basins in which perennially ice-covered lakes are found. One of the most unusual features of these lakes is the occurrence of high O2 concentrations in the water column; values ranging from slightly more than saturation to more than four t...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/325343a0
更新日期:1987-01-22 00:00:00
abstract::In myelinated nerves, segregation of voltage-dependent sodium channels to nodes of Ranvier is crucial for saltatory conduction along axons. As sodium channels associate and colocalize with ankyrin at nodes of Ranvier, one possibility is that sodium channels are recruited and immobilized at axonal sites which are speci...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/356333a0
更新日期:1992-03-26 00:00:00
abstract::The relationship between the semantic processing of words and of pictures is a matter of debate among cognitive scientists. We studied the functional anatomy of such processing by using positron-emission tomography (PET). We contrasted activity during two semantic tasks (probing knowledge of associations between conce...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/383254a0
更新日期:1996-09-19 00:00:00
abstract::The neurohypophysial hormone vasopressin exerts antidiuretic, vasopressor and behavioural effects (for example, facilitation of memory processes). Vasopressin may alter animal behaviour via direct effect on brain processes. Recently, however, it has been suggested that vasopressin acts mainly at peripheral receptor sy...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/308276a0
更新日期:1984-03-15 00:00:00
abstract::Phosphorylation of the carboxy-terminal domain of the largest subunit of RNA polymerase II is believed to control the transition from transcription initiation to elongation. The general transcription factor IIH (TFIIH) contains a kinase activity capable of phosphorylating this domain. Factors that promote the associat...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/358641a0
更新日期:1992-08-20 00:00:00
abstract::Antifreeze proteins provide fish with protection against the freezing effect of polar environments by binding to ice surfaces and inhibiting growth of ice crystals. We present the X-ray crystal structure at 1.5 A resolution of a lone alpha-helical antifreeze protein from winter flounder, which provides a detailed look...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/375427a0
更新日期:1995-06-01 00:00:00
abstract::The assimilation and mineralization of dissolved organic carbon (DOC) by marine bacterioplankton is a major process in the ocean carbon cycle. However, little information exists on the specific metabolic functions of participating bacteria and on whether individual taxa specialize on particular components of the marin...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature06513
更新日期:2008-02-07 00:00:00
abstract::Only a very small fraction of long noncoding RNAs (lncRNAs) are well characterized. The evolutionary history of lncRNAs can provide insights into their functionality, but the absence of lncRNA annotations in non-model organisms has precluded comparative analyses. Here we present a large-scale evolutionary study of lnc...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature12943
更新日期:2014-01-30 00:00:00
abstract::Coronavirus disease 2019 (COVID-19) is a disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in a pandemic1. The C5a complement factor and its receptor C5aR1 (also known as CD88) have a key role in the initiation and maintenance of several inflammatory respons...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-020-2600-6
更新日期:2020-12-01 00:00:00
abstract::Nitrogen enrichment is widely thought to be responsible for the loss of plant species from temperate terrestrial ecosystems. This view is based on field surveys and controlled experiments showing that species richness correlates negatively with high productivity and nitrogen enrichment. However, as the type of nutrien...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature03950
更新日期:2005-09-22 00:00:00
abstract::The mec-2 gene is required for the function of a set of six touch receptor neurons in the nematode Caenorhabditis elegans; mec-2 mutants, which are touch-insensitive, have touch cells that appear morphologically normal. Gene interaction studies suggest that mec-2 positively regulates the activity of the putative mecha...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/378292a0
更新日期:1995-11-16 00:00:00
abstract::In this Article, in Fig. 1a, the 5' and 3' labels were reversed in the DNA sequence, and Fig. 4 was missing panel labels a-e. These errors have been corrected online. ...
journal_title:Nature
pub_type: 已发布勘误
doi:10.1038/s41586-019-1343-8
更新日期:2019-07-01 00:00:00
abstract::The epiblast (EPI) is the origin of all somatic and germ cells in mammals, and of pluripotent stem cells in vitro. To explore the ontogeny of human and primate pluripotency, here we perform comprehensive single-cell RNA sequencing for pre- and post-implantation EPI development in cynomolgus monkeys (Macaca fasciculari...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature19096
更新日期:2016-09-01 00:00:00
abstract::Type III collagen is often found in the same tissues as type I collagen, yet the function and nature of the fibrils formed by the two collagens differ markedly. To understand the evolutionary history of the collagen gene family in more detail, we isolated the gene for type III collagen and compared its structure with ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/310333a0
更新日期:1984-07-26 00:00:00
abstract::Seismological studies have revealed that a complex texture or heterogeneity exists in the Earth's inner core and at the boundary between core and mantle. These studies highlight the importance of understanding the properties of iron when modelling the composition and dynamics of the core and the interaction of the cor...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35087559
更新日期:2001-08-02 00:00:00
abstract::In adult animals, sensory neurons innervating the skin are phenotypically diverse. We have now investigated whether nerve growth factor (NGF) has a physiological role in the development of this diversity. We gave antisera against NGF to rats from postnatal day 1 (PND 1) to adulthood (5 weeks). We found a virtually com...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/350500a0
更新日期:1991-04-11 00:00:00
abstract:: ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/551S40a
更新日期:2017-11-08 00:00:00
abstract::Folding of two monomeric enzymes mediated by groE has been reconstituted in vitro. The groEL protein stabilizes the polypeptides in a conformation resembling the 'molten globule' state. Mg-ATP and groES then promote the acquisition of ordered tertiary structure at the surface of groEL. Folding requires the hydrolysis ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/352036a0
更新日期:1991-07-04 00:00:00
abstract::Plasmodium falciparum infected erythrocytes containing mature trophozoites and schizonts sequester along venular endothelium and are not in the peripheral circulation of patients with malaria. Knobs appear on infected erythrocytes and are the points of attachment to endothelium. Sequestration may protect the parasite ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/318064a0
更新日期:1985-11-07 00:00:00
abstract::Carbonates on large Solar System bodies like Earth and Mars (the latter represented by the meteorite ALH84001) form through the weathering of silicates in a watery (CO3)2- solution. The presence of carbonates in interplanetary dust particles and asteroids (again, represented by meteorites) is not completely understood...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/415295a
更新日期:2002-01-17 00:00:00
abstract::The IKKalpha and IKKbeta catalytic subunits of IkappaB kinase (IKK) share 51% amino-acid identity and similar biochemical activities: they both phosphorylate IkappaB proteins at serines that trigger their degradation. IKKalpha and IKKbeta differ, however, in their physiological functions. IKKbeta and the IKKgamma/NEMO...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35070605
更新日期:2001-04-05 00:00:00
abstract::The central nervous system (CNS) requires a tightly controlled environment free of toxins and pathogens to provide the proper chemical composition for neural function. This environment is maintained by the 'blood-brain barrier' (BBB), which is composed of blood vessels whose endothelial cells display specialized tight...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature13324
更新日期:2014-05-22 00:00:00
abstract::The cyanobacterium Prochlorococcus is the dominant oxygenic phototroph in the tropical and subtropical regions of the world's oceans. It can grow at a range of depths over which light intensities can vary by up to 4 orders of magnitude. This broad depth distribution has been hypothesized to stem from the coexistence o...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/30965
更新日期:1998-06-04 00:00:00
abstract::Concern about the levels of lead in blood is widespread. There is uncertainty, however, about the relative importance of the various environmental sources. Lead in petrol is widely assumed to be one of the most important sources and air and dust have been identified as the main routes to man. Water is regarded as an i...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/310138a0
更新日期:1984-07-12 00:00:00
abstract::The presence of homoeo box sequences in the genomes of vertebrates has suggested that these metazoans possess the equivalent of the homoeotic genes that have a key role in regulating the development of the fruitfly Drosophila melanogaster. We report here that a novel murine homoeo box-containing gene is expressed in e...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/314713a0
更新日期:1985-04-25 00:00:00