ArticleThe Journal of biological chemistry2019
Tissue-specific kinase expression and activity regulate flux through the pyruvate dehydrogenase complex.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Macrophage-associated kinase signaling in atherosclerosis - a systematic review.Cell communication and signaling : CCS · 2026Pooled it
- Regulation of pyruvate dehydrogenase complex: Dancing to different drums in cancer.International journal of cancer · 2026Review
- Daytime-Dependent Effects of Thiamine on the Thiamine Pool and Pyruvate Dehydrogenase Regulation in the Brain and Heart.International journal of molecular sciences · 2025Article
- Hepatic gluconeogenesis and PDK3 upregulation drive cancer cachexia in flies and mice.Nature metabolism · 2025Article
- Pyruvate dehydrogenase kinase 1 controls triacylglycerol hydrolysis in cardiomyocytes.bioRxiv : the preprint server for biology · 2025Article
- Inhibition of the ubiquitin-proteasome system reduces the abundance of pyruvate dehydrogenase kinase 1 in cultured myotubes.Journal of muscle research and cell motility · 2024Article
- Regulation of muscle pyruvate dehydrogenase activity and fuel use during exercise in high-altitude deer mice.The Journal of experimental biology · 2024Article
- Reducing Oxidative Stress and Inflammation by Pyruvate Dehydrogenase Kinase 4 Inhibition Is Important in Prevention of Renal Ischemia-Reperfusion Injury in Diabetic Mice.Diabetes & metabolism journal · 2024Article
- Mitochondrial phosphoproteomes are functionally specialized across tissues.Life science alliance · 2024Article
- Mitochondrial Alpha-Keto Acid Dehydrogenase Complexes: Recent Developments on Structure and Function in Health and Disease.Sub-cellular biochemistry · 2024Review
- Review
- Tumor Cytokine-Induced Hepatic Gluconeogenesis Contributes to Cancer Cachexia: Insights from Full Body Single Nuclei Sequencing.bioRxiv : the preprint server for biology · 2023Article
- Regulation and function of the mammalian tricarboxylic acid cycle.The Journal of biological chemistry · 2023Review
- Pyruvate dehydrogenase kinase supports macrophage NLRP3 inflammasome activation during acute inflammation.Cell reports · 2023Article
- Pyruvate dehydrogenase kinase regulates macrophage polarization in metabolic and inflammatory diseases.Frontiers in immunology · 2023Review
- Inhibition of pyruvate dehydrogenase kinase improves carbohydrate utilization in Nile tilapia by regulating PDK2/4-PDHE1α axis and insulin sensitivity.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2022Article
- Metabolic and Cellular Compartments of Acetyl-CoA in the Healthy and Diseased Brain.International journal of molecular sciences · 2022Review
- Retinoic acid regulates pyruvate dehydrogenase kinase 4 (Pdk4) to modulate fuel utilization in the adult heart: Insights from wild-type and β-carotene 9',10' oxygenase knockout mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Protective effect of natural products in the metabolic-associated kidney diseasesFrontiers in pharmacology · 2022Review
- Multitissue 2H/13C flux analysis reveals reciprocal upregulation of renal gluconeogenesis in hepatic PEPCK-C-knockout mice.JCI insight · 2021Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The pyruvate dehydrogenase complex (PDC) is a multienzyme assembly that converts pyruvate to acetyl-CoA. As pyruvate and acetyl-CoA play central roles in cellular metabolism, understanding PDC regulation is pivotal to understanding the larger metabolic network. The activity of mammalian PDC is regulated through reversible phosphorylation governed by at least four isozymes of pyruvate dehydrogenase kinase (PDK). Deciphering which kinase regulates PDC in organisms at specific times or places has been challenging. In this study, we analyzed mouse strains carrying targeted mutations of individual isozymes to explore their role in regulating PDC activity. Analysis of protein content of PDK isozymes in major metabolic tissues revealed that PDK1 and PDK2 were ubiquitously expressed, whereas PDK3 and PDK4 displayed a rather limited tissue distribution. Measurement of kinase activity showed that PDK1 is the principal isozyme regulating hepatic PDC. PDK2 was largely responsible for inactivation of PDC in tissues of muscle origin and brown adipose tissue (BAT). PDK3 was the principal kinase regulating pyruvate dehydrogenase activity in kidney and brain. In a well-fed state, the tissue levels of PDK4 protein were fairly low. In most tissues tested, PDK4 ablation had little effect on the overall rates of inactivation of PDC in kinase reaction. Taken together, these data strongly suggest that the activity of PDC is regulated by different isozymes in different tissues. Furthermore, it appears that the overall flux through PDC in a given tissue largely reflects the properties of the PDK isozyme that is principally responsible for the regulation of PDC activity in that tissue.
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