ArticleThe EMBO journal2020
Dysfunctional oxidative phosphorylation shunts branched-chain amino acid catabolism onto lipogenesis in skeletal muscle.
Article in The EMBO journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
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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.
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Who cites it
42 citing papers in PubMed, 51 citations in OpenAlex.
- ATPIF1, the rheostat in mitochondrial bioenergetics and dysfunction in diseases.Mitochondrion · 2026Review
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- Metabolic checkpoints in bone remodeling: from dysregulation to targeted therapies.Clinics (Sao Paulo, Brazil) · 2026Review
- Leucine and Valine Improve Pork Tenderness by Driving Myofiber Transition, Optimizing Lipid Profiles and Enhancing Antioxidant Defense.Animals : an open access journal from MDPI · 2026Article
- Serum-Derived Extracellular Vesicles as Biological Indicator of Mobility Resilience in Older Adults.Aging cell · 2026Article
- Lipids grease the chain of cancer progression.Trends in cancer · 2026Review
- Molecular Framework of the Onset and Progression of Skeletal Muscle Aging.International journal of molecular sciences · 2025Review
- Oxidative Phosphorylation in Uncoupled Mitochondria.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Short-term Physical Activity Reduces Metabolic-associated Steatohepatitis by Promoting the Degradation of Branched-chain Amino Acids in Skeletal Muscle.Journal of clinical and translational hepatology · 2025Article
- Integrated proteomic and targeted Next Generation Sequencing reveal relevant heterogeneity in lower-grade meningioma and ANXA3 as a new target in NF2 mutated meningiomas.EBioMedicine · 2025Article
- Reprogramming patient-induced pluripotent stem cell-specific retinal organoids for deciphering epigenetic modifications of RNA methylation.Journal of the Chinese Medical Association : JCMA · 2025Article
- Branched-chain amino acid metabolism: Pathophysiological mechanism and therapeutic intervention in metabolic diseases.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Review
- Comprehensive Review of Sepsis-Related Skeletal Muscle Atrophy: Mechanisms, Diagnosis and Therapeutic Strategies.Journal of inflammation research · 2025Review
- Article
- IF1 is a cold-regulated switch of ATP synthase hydrolytic activity to support thermogenesis in brown fat.The EMBO journal · 2024Article
- Ablation ofiScience · 2024Article
- Review
- An ETFDH-driven metabolon supports OXPHOS efficiency in skeletal muscle by regulating coenzyme Q homeostasis.Nature metabolism · 2024Article
- Early life exposure to vitamin D deficiency impairs molecular mechanisms that regulate liver cholesterol biosynthesis, energy metabolism, inflammation, and detoxification.Frontiers in endocrinology · 2024Article
- COX17 acetylation via MOF-KANSL complex promotes mitochondrial integrity and function.Nature metabolism · 2023Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
It is controversial whether mitochondrial dysfunction in skeletal muscle is the cause or consequence of metabolic disorders. Herein, we demonstrate that in vivo inhibition of mitochondrial ATP synthase in muscle alters whole-body lipid homeostasis. Mice with restrained mitochondrial ATP synthase activity presented intrafiber lipid droplets, dysregulation of acyl-glycerides, and higher visceral adipose tissue deposits, poising these animals to insulin resistance. This mitochondrial energy crisis increases lactate production, prevents fatty acid β-oxidation, and forces the catabolism of branched-chain amino acids (BCAA) to provide acetyl-CoA for de novo lipid synthesis. In turn, muscle accumulation of acetyl-CoA leads to acetylation-dependent inhibition of mitochondrial respiratory complex II enhancing oxidative phosphorylation dysfunction which results in augmented ROS production. By screening 702 FDA-approved drugs, we identified edaravone as a potent mitochondrial antioxidant and enhancer. Edaravone administration restored ROS and lipid homeostasis in skeletal muscle and reinstated insulin sensitivity. Our results suggest that muscular mitochondrial perturbations are causative of metabolic disorders and that edaravone is a potential treatment for these diseases.
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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.