MINI REVIEW article

Front. Physiol.

Sec. Metabolic Physiology

Volume 16 - 2025 | doi: 10.3389/fphys.2025.1596636

Emerging Roles of Pyruvate Dehydrogenase Phosphatase 1: A Key Player in Metabolic Health

Provisionally accepted
  • Wayne State University, Detroit, United States

The final, formatted version of the article will be published soon.

Pyruvate dehydrogenase phosphatase (PDP), a structurally conserved member of the protein phosphatase C family (PP2C) of proteins, is a key regulatory enzyme responsible for reactivation of the mitochondrial gate-keeper, pyruvate dehydrogenase (PDH). Tissue-specific expression of PDP isozymes, specifically PDP1 and PDP2 facilitate regulation of the multi-subunit PDH, influencing flux of substrates to the TCA cycle. PDP1 is a heterodimeric, Ca 2+ sensitive isoform, predominantly expressed in muscle tissue where its role in regulating PDH activity is well established. Emerging research suggests that it is involved in various diseases, including pancreatic ductal adenocarcinoma, cardiomyogenesis defects, traumatic brain injury, and Barth syndrome. In this review, we discuss recent studies revealing the crucial role of PDP1 and its dysregulation in various metabolic disorders, thereby highlighting its potential as a therapeutic target for these debilitating diseases.

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Received: 19 Mar 2025; Accepted: 12 May 2025.

Copyright: © 2025 Kumar and Greenberg. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Miriam L. Greenberg, Wayne State University, Detroit, United States

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