Abstract:
:BAT-controlled thermogenic activity is thought to be required for its capacity to prevent the development of insulin resistance. This hypothesis predicts that mediators of thermogenesis may help prevent diet-induced insulin resistance. We report that the mitochondrial fusion protein Mitofusin 2 (Mfn2) in BAT is essential for cold-stimulated thermogenesis, but promotes insulin resistance in obese mice. Mfn2 deletion in mice through Ucp1-cre (BAT-Mfn2-KO) causes BAT lipohypertrophy and cold intolerance. Surprisingly however, deletion of Mfn2 in mice fed a high fat diet (HFD) results in improved insulin sensitivity and resistance to obesity, while impaired cold-stimulated thermogenesis is maintained. Improvement in insulin sensitivity is associated with a gender-specific remodeling of BAT mitochondrial function. In females, BAT mitochondria increase their efficiency for ATP-synthesizing fat oxidation, whereas in BAT from males, complex I-driven respiration is decreased and glycolytic capacity is increased. Thus, BAT adaptation to obesity is regulated by Mfn2 and with BAT-Mfn2 absent, BAT contribution to prevention of insulin resistance is independent and inversely correlated to whole-body cold-stimulated thermogenesis.
journal_name
EMBO Repjournal_title
EMBO reportsauthors
Mahdaviani K,Benador IY,Su S,Gharakhanian RA,Stiles L,Trudeau KM,Cardamone M,Enríquez-Zarralanga V,Ritou E,Aprahamian T,Oliveira MF,Corkey BE,Perissi V,Liesa M,Shirihai OSdoi
10.15252/embr.201643827subject
Has Abstractpub_date
2017-07-01 00:00:00pages
1123-1138issue
7eissn
1469-221Xissn
1469-3178pii
embr.201643827journal_volume
18pub_type
杂志文章相关文献
EMBO REPORTS文献大全abstract::Defects in protein folding and the proteasomal pathway have been linked with many neurodegenerative diseases. PLIC-1 (protein linking IAP to the cytoskeleton) is a ubiquitin-like protein that binds to the ubiquitin-interacting motif (UIM) of the proteasomal subunit S5a. Here, we show that PLIC-1 also binds to the UIM ...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/sj.embor.7400823
更新日期:2006-12-01 00:00:00
abstract::The intracellular modification of proteins by the addition of a single O-linked N-acetylglucosamine (O-GlcNAc) molecule is a ubiquitous post-translational modification in eukaryotic cells. It is catalysed by O-linked N-acetylglucosaminyltransferase, which attaches O-GlcNAc to serine/threonine residues, and it is count...
journal_title:EMBO reports
pub_type: 杂志文章,评审
doi:10.1038/embor.2008.129
更新日期:2008-08-01 00:00:00
abstract::Growth plasticity is a key mechanism by which plants adapt to the ever-changing environmental conditions. Since growth is a high-energy-demanding and irreversible process, it is expected to be regulated by the integration of endogenous energy status as well as environmental conditions. Here, we show that trehalose-6-p...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201947828
更新日期:2019-10-04 00:00:00
abstract::HOIL-1L and its binding partner HOIP are essential components of the E3-ligase complex that generates linear ubiquitin (Ub) chains, which are critical regulators of NF-κB activation. Using crystallographic and mutational approaches, we characterize the unexpected structural basis for the specific interaction between t...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/embor.2012.24
更新日期:2012-05-01 00:00:00
abstract::The cytosolic pathogen sensor RIG-I is activated by RNAs with exposed 5'-triphosphate (5'-ppp) and terminal double-stranded structures, such as those that are generated during viral infection. RIG-I has been shown to translocate on dsRNA in an ATP-dependent manner. However, the precise role of the ATPase activity in R...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/embor.2013.102
更新日期:2013-09-01 00:00:00
abstract::Understanding how cell fate decisions are regulated is a fundamental goal of developmental and stem cell biology. Most studies on the control of cell fate decisions address the contributions of changes in transcriptional programming, epigenetic modifications, and biochemical differentiation cues. However, recent studi...
journal_title:EMBO reports
pub_type: 杂志文章,评审
doi:10.15252/embr.201744816
更新日期:2017-12-01 00:00:00
abstract::SUMOylation is a post-translational modification that positively regulates monoallelic expression of the trypanosome variant surface glycoprotein (VSG). The presence of a highly SUMOylated focus associated with the nuclear body, where the VSG gene is transcribed, further suggests an important role of SUMOylation in re...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201948029
更新日期:2019-12-05 00:00:00
abstract::Short interfering RNAs (siRNAs) are short (21-23 nt) double-stranded RNAs that direct the sequence-specific degradation of corresponding mRNAs, resulting in suppression of gene activity. siRNAs are powerful tools for gene functional analysis in mammals. Chemically synthesized siRNAs permit transient gene repression bu...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/sj.embor.7400064
更新日期:2004-02-01 00:00:00
abstract::The major DNA methyltransferase, Dnmt1, associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand. In view of the slow kinetics of Dnmt1 in vitro versus the fast progression of the replication fork, we have tested whether Dnmt1 associates with chromatin beyond...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/sj.embor.7400295
更新日期:2004-12-01 00:00:00
abstract::MicroRNAs (miRNAs) regulate target mRNAs by silencing them. Reciprocally, however, target mRNAs can also modulate miRNA stability. Here, we uncover a remarkable efficacy of target RNA-directed miRNA degradation (TDMD) in rodent primary neurons. Coincident with degradation, and while still bound to Argonaute, targeted ...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201540078
更新日期:2015-04-01 00:00:00
abstract::Autophagosome formation is promoted by the PI3 kinase complex and negatively regulated by myotubularin phosphatases, indicating that regulation of local phosphatidylinositol 3-phosphate (PtdIns3P) levels is important for this early phase of autophagy. Here, we show that the Caenorhabditis elegans myotubularin phosphat...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201438618
更新日期:2014-09-01 00:00:00
abstract::Synaptic mitochondria are particularly vulnerable to physiological insults, and defects in synaptic mitochondria are linked to early pathophysiology of Alzheimer's disease (AD). Mitophagy, a cargo-specific autophagy for elimination of dysfunctional mitochondria, constitutes a key quality control mechanism. However, ho...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201949801
更新日期:2020-09-03 00:00:00
abstract::Very little is known about the biogenesis and assembly of oligomeric membrane proteins. In this study, the biogenesis of KcsA, a prokaryotic homotetrameric potassium channel, is investigated. Using in vivo pulse-chase experiments, both the monomeric and tetrameric form could be identified. The conversion of monomers i...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1093/embo-reports/kvd067
更新日期:2000-10-01 00:00:00
abstract::Differentiation of most cell types requires both establishment of G1 arrest and the induction of a program related to achieving quiescence. We have chosen to study the differentiation of oligodendrocyte cells to determine the role of p27 and p21 in this process. Here we report that both p27 and p21 are required for th...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1093/embo-reports/kve008
更新日期:2001-01-01 00:00:00
abstract::gamma-Secretase-dependent regulated intramembrane proteolysis of amyloid precursor protein (APP) releases the APP intracellular domain (AICD). The question of whether this domain, like the Notch intracellular domain, is involved in nuclear signalling is highly controversial. Although some reports suggest that AICD reg...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/sj.embor.7400704
更新日期:2006-07-01 00:00:00
abstract::The hypoxic response in humans is mediated by the hypoxia-inducible transcription factor (HIF), for which prolyl hydroxylases (PHDs) act as oxygen-sensing components. The evolutionary origins of the HIF system have been previously unclear. We demonstrate a functional HIF system in the simplest animal, Trichoplax adhae...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/embor.2010.170
更新日期:2011-01-01 00:00:00
abstract::The ubiquitin-binding zinc finger (UBZ) domain of human DNA Y-family polymerase (pol) eta is important in the recruitment of the polymerase to the stalled replication machinery in translesion synthesis. Here, we report the solution structure of the pol eta UBZ domain and its interaction with ubiquitin. We show that th...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/sj.embor.7400901
更新日期:2007-03-01 00:00:00
abstract::One limitation for the study of chromosomal fragile sites is that they must be studied on metaphase spreads, after the breakage. We show here that bacterial lac operator (lacO) repeats are prone to spontaneous breakage, which when combined with a fluorescent lac repressor (lacR) has allowed us to track a fragile site ...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/embor.2011.158
更新日期:2011-09-30 00:00:00
abstract::Elongation of the telomeric overhang by telomerase is counteracted by synthesis of the complementary strand by the CST complex, CTC1(Cdc13)/Stn1/Ten1. Interaction of budding yeast Stn1 with overhang-binding Cdc13 is increased by Cdc13 SUMOylation. Human and fission yeast CST instead interact with overhang-binding TPP1...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201438919
更新日期:2014-08-01 00:00:00
abstract::Mutations in TRPML1 cause the lysosomal storage disease mucolipidosis type IV (MLIV). The role of TRPML1 in cell function and how the mutations cause the disease are not well understood. Most studies focus on the role of TRPML1 in constitutive membrane trafficking to and from the lysosomes. However, this cannot explai...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201541542
更新日期:2016-02-01 00:00:00
abstract::Hydrogen sulfide (H2 S), an endogenous signaling gaseous molecule, is involved in various physiological activities, including vessel relaxation, regulation of cellular bioenergetics, inflammation, and angiogenesis. By using xenograft orthotopic implantation of prostate cancer PC3 cells and subsequently comparing bone ...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201845986
更新日期:2019-10-04 00:00:00
abstract::The ubiquitin ligase Highwire restrains synaptic growth and promotes evoked neurotransmission at NMJ synapses in Drosophila Highwire regulates synaptic morphology by downregulating the MAP3K Wallenda, but excess Wallenda signaling does not account for the decreased presynaptic release observed in highwire mutants. Hen...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201846975
更新日期:2019-03-01 00:00:00
abstract::Endogenous retroviruses (ERVs) have accumulated in vertebrate genomes and contribute to the complexity of gene regulation. KAP1 represses ERVs during development by its recruitment to their repetitive sequences through KRAB zinc-finger proteins (KZNFs), but little is known about the regulation of ERVs in adult tissues...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201745000
更新日期:2018-10-01 00:00:00
abstract::Phosphoinositides have crucial roles in cellular controls, many of which have been established through the use of small-molecule inhibitors. Here, we describe YM201636, a potent inhibitor of the mammalian class III phosphatidylinositol phosphate kinase PIKfyve, which synthesizes phosphatidylinositol 3,5-bisphosphate. ...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1038/sj.embor.7401155
更新日期:2008-02-01 00:00:00
abstract::Biasing the sex ratio of populations of different organisms, including plants, insects, crustacean, and fish, has been demonstrated by genetic and non-genetic approaches. However, biasing the sex ratio of mammalian populations has not been demonstrated genetically. Here, we provide a first proof of concept for such a ...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201948269
更新日期:2019-08-01 00:00:00
abstract::The denitrosylase S-nitrosoglutathione reductase (GSNOR) has been suggested to sustain mitochondrial removal by autophagy (mitophagy), functionally linking S-nitrosylation to cell senescence and aging. In this study, we provide evidence that GSNOR is induced at the translational level in response to hydrogen peroxide ...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.202050500
更新日期:2020-11-27 00:00:00
abstract::Alternative RNA processing of LMNA pre-mRNA produces three main protein isoforms, that is, lamin A, progerin, and lamin C. De novo mutations that favor the expression of progerin over lamin A lead to Hutchinson-Gilford progeria syndrome (HGPS), providing support for the involvement of LMNA processing in pathological a...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1002/embr.201338126
更新日期:2014-05-01 00:00:00
abstract::Like many transcription regulators, histone methyltransferases G9a and G9a-like protein (GLP) can act gene-specifically as coregulators, but mechanisms controlling this specificity are mostly unknown. We show that adjacent post-translational methylation and phosphorylation regulate binding of G9a and GLP to heterochro...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.15252/embr.201744060
更新日期:2017-08-01 00:00:00
abstract::Loss of primary cilia is a key feature of von Hippel-Lindau tumor suppressor (VHL)-associated pathology. Although VHL-deficiency predisposes cells to precipitous cilia disassembly in response to growth factor cues, it does not affect ciliogenesis. Here, using a siRNA-based screen to find genes that are essential for c...
journal_title:EMBO reports
pub_type: 杂志文章
doi:10.1002/embr.201337688
更新日期:2014-01-01 00:00:00
abstract::The EMBO conference 'From Structure to Function of Translocation Machines' took place in April 2013 in Dubrovnik, Croatia. The meeting brought together a mix of established and aspiring researchers to discuss a wealth of unpublished data and ideas in a lively scientific programme of talks designed to shatter the estab...
journal_title:EMBO reports
pub_type:
doi:10.1038/embor.2013.79
更新日期:2013-07-01 00:00:00