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Lung dendritic-cell metabolism underlies susceptibility to viral infection in diabetes
Hyperglycaemia leads to impaired costimulatory molecule expression, antigen transport and T cell priming in distinct lung dendritic cell subsets, driving a defective antiviral adaptive immune response, delayed viral clearance and enhanced mortality.
- Samuel Philip Nobs
- , Aleksandra A. Kolodziejczyk
- & Eran Elinav
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Article |
HRG-9 homologues regulate haem trafficking from haem-enriched compartments
HRG-9 (also known as TANGO2) is an evolutionarily conserved haem chaperone that traffics haem from sites of storage or synthesis in eukaryotic cells.
- Fengxiu Sun
- , Zhenzhen Zhao
- & Caiyong Chen
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Article |
Defining mitochondrial protein functions through deep multiomic profiling
A multiomics resource characterizing human mitochondrial proteins enables identification of biological functions and supports genetic diagnosis of mitochondrial pathologies.
- Jarred W. Rensvold
- , Evgenia Shishkova
- & David J. Pagliarini
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Article |
Gut microbiota modulates weight gain in mice after discontinued smoke exposure
A study of mice exposed to cigarette smoke suggests that smoking-cessation-induced weight gain is associated with a dysbiotic state that is driven by smoking-related metabolites.
- Leviel Fluhr
- , Uria Mor
- & Eran Elinav
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Article |
Structural basis of inhibition of the human SGLT2–MAP17 glucose transporter
Using cryogenic electron microscopy, the structure of the human SGLT2–MAP17 complex captured in the empagliflozin-bound state reveals the inhibitory mechanism of these anti-diabetic drugs.
- Yange Niu
- , Rui Liu
- & Lei Chen
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Article |
MFSD12 mediates the import of cysteine into melanosomes and lysosomes
A rapid labelling and immunopurification-based method is used to isolate melanosomes and profile their labile metabolites, revealing that MFSD12 has a key role in cysteine import into melanosomes and lysosomes.
- Charles H. Adelmann
- , Anna K. Traunbauer
- & David M. Sabatini
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Article |
Feeding induces cholesterol biosynthesis via the mTORC1–USP20–HMGCR axis
mTORC1 stabilizes HMG-CoA reductase, a rate-limiting enzyme in the cholesterol biosynthesis pathway, via the deubiquitylase USP20 in response to feeding.
- Xiao-Yi Lu
- , Xiong-Jie Shi
- & Bao-Liang Song
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Letter |
Mitochondrial translation requires folate-dependent tRNA methylation
Mammalian mitochondria use folate-bound one-carbon units generated by the enzyme SHMT2 to methylate tRNA, and this modification is required for mitochondrial translation and thus oxidative phosphorylation.
- Raphael J. Morscher
- , Gregory S. Ducker
- & Joshua D. Rabinowitz
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Letter |
Genome-wide associations for birth weight and correlations with adult disease
Multi-ancestry genome-wide association analyses for birth weight in 153,781 individuals identified 60 genomic loci in which birth weight and fetal genotype were associated and found an inverse genetic correlation between birth weight and cardiometabolic risk.
- Momoko Horikoshi
- , Robin N. Beaumont
- & Rachel M. Freathy
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Article |
Crystal structure of the human glucose transporter GLUT1
The structure of human GLUT1 in an inward-open conformation is reported; access to the structure of the human protein, instead of just a bacterial homologue, made it possible to map (inactivating) mutations associated with GLUT1 deficiency syndrome onto the structure.
- Dong Deng
- , Chao Xu
- & Nieng Yan
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News & Views |
Time in a bottle
A biological clock synchronizes animal behaviour and physiology with Earth's 24-hour rotation. Drugs targeting the clock's 'gears' show promise for treating obesity and other metabolic disorders. See Article p.62 & Letter p.123
- Joseph Bass
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Correspondence |
Sugar: a problem of developed countries
- Christiani Jeyakumar Henry
- & Viren Ranawana
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Letter |
Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides
- Katey J. Rayner
- , Christine C. Esau
- & Kathryn J. Moore
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Letter |
Endonuclease G is a novel determinant of cardiac hypertrophy and mitochondrial function
- Chris McDermott-Roe
- , Junmei Ye
- & Stuart A. Cook
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Letter |
Dynamics of human adipose lipid turnover in health and metabolic disease
- Peter Arner
- , Samuel Bernard
- & Kirsty L. Spalding
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Inside View |
Inside View: Pfizer
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Review Article |
Molecular chaperones in protein folding and proteostasis
- F. Ulrich Hartl
- , Andreas Bracher
- & Manajit Hayer-Hartl
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Research Highlights |
Bad fat makes good
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News & Views |
A platform for copper pumps
Copper is vital to most cells, but too much is lethal. The structure of a protein that pumps copper ions out of the cytosol provides insight into both the pumping mechanism and how certain mutations in the protein cause disease. See Article p.59
- Nigel J. Robinson
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News & Views |
A lipid for fat disorders
A high-fat diet often leads to metabolic disorders such as diabetes, fatty liver disease and obesity. One lipid, however, might mitigate these effects through an unexpected signalling role in the nucleus. See Letter p.506
- Holly A. Ingraham
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Letter |
A nuclear-receptor-dependent phosphatidylcholine pathway with antidiabetic effects
- Jae Man Lee
- , Yoon Kwang Lee
- & David D. Moore
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Article |
Telomere dysfunction induces metabolic and mitochondrial compromise
Here it is shown that telomere dysfunction drives metabolic and mitochondrial compromise. Mice with dysfunctional telomeres activate p53, which in turn represses PGC-1α and PGC-1β, master regulators of metabolic and mitochondrial processes. This results in reduced mitochondrial mass, mitochondrial dysfunction and reduced ATP generation, impaired gluconeogenesis, cariomyopathy and increased reactive oxygen species. This telomere–p53–PGC pathway shows how telomere dysfunction may compromise organ function and contribute to age-related disorders.
- Ergün Sahin
- , Simona Colla
- & Ronald A. DePinho
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Letter |
A role for mitochondria in NLRP3 inflammasome activation
Mitochondrial reactive oxygen species are shown to be required for activation of the NLRP3 inflammasome by various stimuli.
- Rongbin Zhou
- , Amir S. Yazdi
- & Jürg Tschopp
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News & Views |
Fathers' nutritional legacy
A female can develop a diabetes-like disease due to a high fat content in her father's diet before she was conceived. Epigenetic modifications of the father's sperm DNA might underlie this peculiar observation. See Letter p.963
- Michael K. Skinner
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Letter |
Antibodies to human serum amyloid P component eliminate visceral amyloid deposits
Systemic amyloidosis is a serious disease caused by accumulation of amyloid fibrils in the viscera and connective tissues. Serum amyloid P component (SAP) is a normal plasma protein that concentrates within the amyloid deposits. These authors find that a combination of a drug that depletes circulating SAP and an antibody that targets residual SAP within the deposits results in clearance of amyloid deposits in a mouse model of the disease.
- Karl Bodin
- , Stephan Ellmerich
- & Mark B. Pepys
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News |
Cot death victims make less serotonin
Mysterious infant deaths linked to chemical deficiency.
- Heidi Ledford
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Research Highlights |
Biochemistry: Designer label
Ancestral allele of DNA polymerase gamma modifies antiviral tolerance
Circadian topology of metabolism