ArticleNature metabolism2025
2-hydroxyglutarate mediates whitening of brown adipocytes coupled to nuclear softening upon mitochondrial dysfunction.
Article in Nature metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
10 citing papers in PubMed.
- Pharmacological inhibition of CLPP stabilizes LETMD1 to boost thermogenesis and alleviate obesity.Adipocyte · 2026Article
- Polyunsaturated fatty acid sequestration protects against mitochondrial dysfunction-induced ferroptosis.EMBO reports · 2026Article
- 2-Hydroxyglutarate Redirects Fatty Acid Partitioning to Mitigate Lipotoxic Stress and Preserve Metabolic Fuel.bioRxiv : the preprint server for biology · 2026Article
- Reprogramming in delipidated adipocytes: metabolism, regulation and progress.Cell death discovery · 2026Review
- Gut microbiota, brown adipose tissue whitening, and obesity: nutritional modulators and metabolic crosstalk.Nutrition & metabolism · 2026Review
- Cordycepin Ameliorates Constant Light-Induced Thermogenic Dysfunction in Brown Adipose Tissue by Activating SIRT1-Mediated Mitochondrial Homeostasis.International journal of molecular sciences · 2026Article
- The depletion of serine beta-lactamase-like protein (LACTB) ameliorates metabolic dysfunction-associated steatotic liver disease by reducing ubiquitin-mediated degradation of carnitine palmitoyltransferase 2.Diabetes, obesity & metabolism · 2026Article
- Decoding Adipose Tissue Phenotypic Switching: From Mechanisms to Computational Drug Discovery.Current obesity reports · 2026Review
- Thyroid Hormone Receptor β1 and PGC1α Coordinately Regulate OPA1/MFN2-Mediated Mitochondrial Fusion and UCP1-Mediated Lipid Browning in ccRCC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- 2-hydroxyglutarate mediates whitening of brown adipocytes coupled to nuclear softening upon mitochondrial dysfunction.Nature metabolism · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
28 authors.
Funding
Abstract
Mitochondria have a crucial role in regulating cellular homeostasis in response to intrinsic and extrinsic cues by changing cellular metabolism to meet these challenges. However, the molecular underpinnings of this regulation and the complete spectrum of these physiological outcomes remain largely unexplored. In this study, we elucidate the mechanisms driving the whitening phenotype in brown adipose tissue (BAT) deficient in the mitochondrial matrix protease CLPP. Here we show that CLPP-deficient BAT shows aberrant accumulation of lipid droplets, which occurs independently of defects in oxygen consumption and fatty acid oxidation. Our results indicate that mitochondrial dysfunction due to CLPP deficiency leads to the build-up of the oncometabolite D-2-hydroxyglutarate (D-2HG), which in turn promotes lipid droplet enlargement. We further demonstrate that D-2HG influences gene expression and decreases nuclear stiffness by modifying epigenetic signatures. We propose that lipid accumulation and altered nuclear stiffness regulated through 2HG are stress responses to mitochondrial dysfunction in BAT.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.