ArticleDiabetologia2010
Human ATP synthase beta is phosphorylated at multiple sites and shows abnormal phosphorylation at specific sites in insulin-resistant muscle.
Article in Diabetologia, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled it.
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
35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 70 citations in OpenAlex.
- A Systematic Review of Proteomics in Obesity: Unpacking the Molecular Puzzle.Current obesity reports · 2024Pooled it
- Common variation in oxidative phosphorylation genes is not a major cause of insulin resistance or type 2 diabetes.Diabetologia · 2012Pooled it
- Trial
- Article
- Mitochondrial heterogeneity in diseases.Signal transduction and targeted therapy · 2023Review
- Article
- Personalized phosphoproteomics identifies functional signaling.Nature biotechnology · 2022Article
- (Dys)regulation of Protein Metabolism in Skeletal Muscle of Humans With Obesity.Frontiers in physiology · 2022Review
- Chronic Activation of AMPK Induces Mitochondrial Biogenesis through Differential Phosphorylation and Abundance of Mitochondrial Proteins inInternational journal of molecular sciences · 2021Article
- Multi-omics profiling: the way towards precision medicine in metabolic diseases.Journal of molecular cell biology · 2021Article
- Mitochondrial Kinases and the Role of Mitochondrial Protein Phosphorylation in Health and Disease.Life (Basel, Switzerland) · 2021Review
- Natural products and other inhibitors of FEuropean journal of medicinal chemistry · 2020Review
- The Mitochondrial Proteomic Signatures of Human Skeletal Muscle Linked to Insulin Resistance.International journal of molecular sciences · 2020Review
- Mitochondrial ATP synthase β-subunit production rate and ATP synthase specific activity are reduced in skeletal muscle of humans with obesity.Experimental physiology · 2019Article
- Orchestration of protein acetylation as a toggle for cellular defense and virus replication.Nature communications · 2018Article
- Gender-effect on the contractile properties of skeletal muscle in streptozotocin-induced diabetic rats.Journal of musculoskeletal & neuronal interactions · 2018Article
- Investigation of post-translational modifications in type 2 diabetes.Clinical proteomics · 2018Review
- A Therapeutic Connection between Dietary Phytochemicals and ATP Synthase.Current medicinal chemistry · 2017Review
- Mitochondrial HDiabetologia · 2017Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisInsulin resistance in skeletal muscle is linked to mitochondrial dysfunction in obesity and type 2 diabetes. Emerging evidence indicates that reversible phosphorylation regulates oxidative phosphorylation (OxPhos) proteins. The aim of this study was to identify and quantify site-specific phosphorylation of the catalytic beta subunit of ATP synthase (ATPsyn-beta) and determine protein abundance of ATPsyn-beta and other OxPhos components in skeletal muscle from healthy and insulin-resistant individuals.
methodsSkeletal muscle biopsies were obtained from lean, healthy, obese, non-diabetic and type 2 diabetic volunteers (each group n = 10) for immunoblotting of proteins, and hypothesis-driven identification and quantification of phosphorylation sites on ATPsyn-beta using targeted nanospray tandem mass spectrometry. Volunteers were metabolically characterised by euglycaemic-hyperinsulinaemic clamps.
resultsSeven phosphorylation sites were identified on ATPsyn-beta purified from human skeletal muscle. Obese individuals with and without type 2 diabetes were characterised by impaired insulin-stimulated glucose disposal rates, and showed a approximately 30% higher phosphorylation of ATPsyn-beta at Tyr361 and Thr213 (within the nucleotide-binding region of ATP synthase) as well as a coordinated downregulation of ATPsyn-beta protein and other OxPhos components. Insulin increased Tyr361 phosphorylation of ATPsyn-beta by approximately 50% in lean and healthy, but not insulin-resistant, individuals. CONCLUSIONS/
interpretationThese data demonstrate that ATPsyn-beta is phosphorylated at multiple sites in human skeletal muscle, and suggest that abnormal site-specific phosphorylation of ATPsyn-beta together with reduced content of OxPhos proteins contributes to mitochondrial dysfunction in insulin resistance. Further characterisation of phosphorylation of ATPsyn-beta may offer novel targets of treatment in human diseases with mitochondrial dysfunction, such as diabetes.
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.