ArticleCell reports2021
PHDs/CPT1B/VDAC1 axis regulates long-chain fatty acid oxidation in cardiomyocytes.
Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 32 citations in OpenAlex.
- Sirt5 preserves mitochondrial homeostasis to improve cardiac function in ischemia-reperfusion injury by inhibiting ANT2 lysine lactylation modification.Cellular and molecular life sciences : CMLS · 2026Article
- Virgin Coconut Oil Attenuates Diabetic Kidney Disease via Gut Microbiota-Metabolism-Inflammation Axis Modulation in Type 2 Diabetic Mice.Food science & nutrition · 2026Article
- Metabolic inflexibility across heart failure phenotypes: mechanisms and type-specific therapeutic implications.Apoptosis : an international journal on programmed cell death · 2026Review
- Multi-omics dissection of heat stress reveals CIITA as a central regulator of metabolic thermotolerance in cattle (Bos taurus).Communications biology · 2026Article
- CPT1B K321 crotonylation contributes to cardiac dysfunction in endotoxic shock.Experimental & molecular medicine · 2026Article
- HIF-mediated hierarchical hypoxic adaptation, a novel paradigm in heart failure pathogenesis: is there a role for targeted therapies?Frontiers in pharmacology · 2026Review
- Novel therapeutic strategies for targeting fatty acid oxidation in cancer.Biomarker research · 2025Review
- The TEX44-CPT1B axis regulates mitochondrial sheath assembly and fatty acid oxidation in sperm.Nature communications · 2025Article
- Combined Effects of Ketogenic Diet and Aerobic Exercise on Skeletal Muscle Fiber Remodeling and Metabolic Adaptation in Simulated Microgravity Mice.Metabolites · 2025Article
- PKN2 enhances the immunosuppressive activity of polymorphonuclear myeloid-derived suppressor cells in esophageal carcinoma by mediating fatty acid oxidation.Molecular medicine (Cambridge, Mass.) · 2025Article
- Sex Differences in Response to Diet Enriched With Glutathione Precursors in the Aging Heart.The journals of gerontology. Series A, Biological sciences and medical sciences · 2025Article
- α-Mangostin prevents diabetic cardiomyopathy by inhibiting oxidative damage and lipotoxicity through the AKT-FOXO1-CD36 pathway.Frontiers in pharmacology · 2025Article
- Mitochondrial SIRT2-mediated CPT2 deacetylation prevents diabetic cardiomyopathy by impeding cardiac fatty acid oxidation.International journal of biological sciences · 2025Article
- Transcriptome Analysis of Myocardial Ischemic-Hypoxic Injury in Rats and Hypoxic H9C2 Cells.ESC heart failure · 2024Article
- The ZNF263/CPT1B axis regulates fatty acid β-oxidation to affect cisplatin resistance in lung adenocarcinoma.The pharmacogenomics journal · 2024Article
- Article
- Sex differences in metabolic adaptation in infants with cyanotic congenital heart disease.Pediatric research · 2024Article
- Intermedin Alleviates Diabetic Cardiomyopathy by Up-Regulating CPT-1β through Activation of the Phosphatidyl Inositol 3 Kinase/Protein Kinase B Signaling Pathway.Pharmaceuticals (Basel, Switzerland) · 2024Article
- MT1G induces lipid droplet accumulation through modulation of H3K14 trimethylation accelerating clear cell renal cell carcinoma progression.British journal of cancer · 2024Article
- Postcontraction [acetylcarnitine] reflects interindividual variation in skeletal muscle ATP production patterns in vivo.American journal of physiology. Regulatory, integrative and comparative physiology · 2024Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Cardiac metabolism is a high-oxygen-consuming process, showing a preference for long-chain fatty acid (LCFA) as the fuel source under physiological conditions. However, a metabolic switch (favoring glucose instead of LCFA) is commonly reported in ischemic or late-stage failing hearts. The mechanism regulating this metabolic switch remains poorly understood. Here, we report that loss of PHD2/3, the cellular oxygen sensors, blocks LCFA mitochondria uptake and β-oxidation in cardiomyocytes. In high-fat-fed mice, PHD2/3 deficiency improves glucose metabolism but exacerbates the cardiac defects. Mechanistically, we find that PHD2/3 bind to CPT1B, a key enzyme of mitochondrial LCFA uptake, promoting CPT1B-P295 hydroxylation. Further, we show that CPT1B-P295 hydroxylation is indispensable for its interaction with VDAC1 and LCFA β-oxidation. Finally, we demonstrate that a CPT1B-P295A mutant constitutively binds to VDAC1 and rescues LCFA metabolism in PHD2/3-deficient cardiomyocytes. Together, our data identify an oxygen-sensitive regulatory axis involved in cardiac metabolism.
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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.