Role of the Pyruvate Dehydrogenase Complex in Metabolic Remodeling: Differential Pyruvate Dehydrogenase Complex Functions in Metabolism.
- Author:
Sungmi PARK
1
;
Jae Han JEON
;
Byong Keol MIN
;
Chae Myeong HA
;
Themis THOUDAM
;
Bo Yoon PARK
;
In Kyu LEE
Author Information
- Publication Type:Review
- Keywords: Glycolysis; Metabolism; Mitochondria; Oxidative phosphorylation
- MeSH: Acetylation; Amino Acids; Citric Acid Cycle; Diabetes Mellitus, Type 2; Fatty Acids; Glucose; Glycolysis; Metabolic Diseases; Metabolic Networks and Pathways; Metabolism*; Mitochondria; Neurodegenerative Diseases; Obesity; Oxidative Phosphorylation; Oxidoreductases; Phosphoric Monoester Hydrolases; Phosphorylation; Phosphotransferases; Protein Processing, Post-Translational; Pyruvate Dehydrogenase Complex*; Pyruvic Acid*
- From:Diabetes & Metabolism Journal 2018;42(4):270-281
- CountryRepublic of Korea
- Language:English
- Abstract: Mitochondrial dysfunction is a hallmark of metabolic diseases such as obesity, type 2 diabetes mellitus, neurodegenerative diseases, and cancers. Dysfunction occurs in part because of altered regulation of the mitochondrial pyruvate dehydrogenase complex (PDC), which acts as a central metabolic node that mediates pyruvate oxidation after glycolysis and fuels the Krebs cycle to meet energy demands. Fine-tuning of PDC activity has been mainly attributed to post-translational modifications of its subunits, including the extensively studied phosphorylation and de-phosphorylation of the E1α subunit of pyruvate dehydrogenase (PDH), modulated by kinases (pyruvate dehydrogenase kinase [PDK] 1-4) and phosphatases (pyruvate dehydrogenase phosphatase [PDP] 1-2), respectively. In addition to phosphorylation, other covalent modifications, including acetylation and succinylation, and changes in metabolite levels via metabolic pathways linked to utilization of glucose, fatty acids, and amino acids, have been identified. In this review, we will summarize the roles of PDC in diverse tissues and how regulation of its activity is affected in various metabolic disorders.
