Subject    :    [2018 Aug;42(4)] Role of the Pyruvate Dehydrogenase Complex in Metabolic Remodeling: Differential Pyruvate Dehydrogenase Complex Functions in Metabolism
Writer KDA
Date 2019-03-06 09:52:46 Hit 206
Diabetes Metab J. 2018 Aug;42(4):270-281. English.
Published online Aug 21, 2018.  https://doi.org/10.4093/dmj.2018.0101 
Copyright © 2018 Korean Diabetes Association
   
Role of the Pyruvate Dehydrogenase Complex in Metabolic Remodeling: Differential Pyruvate Dehydrogenase Complex Functions in Metabolism
Sungmi Park,1 Jae-Han Jeon,2 Byong-Keol Min,3 Chae-Myeong Ha,3 Themis Thoudam,3 Bo-Yoon Park,3 and In-Kyu Lee1,2,3
1Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu, Korea.
2Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea.
3Department of Biomedical Science & BK21 plus KNU Biomedical Convergence Programs, Kyungpook National University, Daegu, Korea.

Corresponding author: In-Kyu Lee. Department of Internal Medicine, School of Medicine, Kyungpook National University, 130 Dongdeok-ro, Jung-gu, Daegu 41944, Korea. Email: leei@knu.ac.kr Corresponding author: Sungmi Park. Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, 807 Hoguk-ro, Buk-gu, Daegu 41404, Korea. Email: smpark93@gmail.com 
 
Received June 17, 2018; Accepted July 05, 2018.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

 
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.

   
Keywords:
GlycolysisMetabolismMitochondriaOxidative phosphorylation
 

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