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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 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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http://dx.doi.org/10.3389/fphys.2025.1596636 | DOI Listing |
Medicine (Baltimore)
September 2025
Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.
Dichloroacetate (DCA), as a pan-inhibitor of pyruvate dehydrogenase kinase, plays a crucial role in energy metabolism and mitochondrial function. DCA decreases lactic acid synthesis, enhances mitochondrial oxidative phosphorylation, and regulates aerobic glycolysis. During the last decade, more and more studies have found that disorders of energy metabolism and mitochondrial dysfunction play a pivotal role in the development and progression of various diseases, and the role of DCA in cancer, metabolic diseases, and inflammatory diseases has been extensively explored in both basic and clinical studies.
View Article and Find Full Text PDFSteroids
September 2025
Department of Physiology, University of Ilorin, Ilorin, Nigeria.
Background: Emerging evidence indicates that metformin-based combination therapy may offer better glycemic control and improved tolerability compared to diabetes monotherapy. Building on this, vitamin D was considered a potential adjunct to metformin for managing type 2 diabetes. Although vitamin D is primarily recognized for its role in calcium regulation, it also appears to influence glucose metabolism and other non-skeletal functions.
View Article and Find Full Text PDFCisplatin resistance significantly limits the efficacy of chemotherapy in non-small cell lung cancer, necessitating the development of new strategies to overcome this barrier. This in vitro study aimed to elucidate the mechanism by which β-Ele reverses cisplatin resistance in lung adenocarcinoma cells via the LINC00511-mediated glycolysis and Wnt/β-catenin signaling pathways. The cisplatin-resistant human lung adenocarcinoma cell line (A549/DDP), with either LINC00511 overexpression or knockdown, was established through plasmid transfection.
View Article and Find Full Text PDFFront Cell Dev Biol
August 2025
Department of Oncology Science, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States.
The Wnt pathway is an evolutionarily conserved signaling cascade that regulates a wide range of fundamental cellular processes, including proliferation, differentiation, polarity, migration, metabolism, and survival. Due to its central regulatory roles, Wnt signaling is critically involved in the pathophysiology of numerous human diseases. Aberrant activation or insufficient inhibition of this pathway has been causally linked to cancer, degenerative disorders, metabolic syndromes, and developmental abnormalities.
View Article and Find Full Text PDFCurr Opin Rheumatol
September 2025
Yale School of Medicine, Department of Internal Medicine, Section of Digestive Diseases, New Haven, Connecticut, USA.
Purpose Of Review: To synthesize current knowledge on the genetic, immunopathogenic, and clinical presentations of systemic sclerosis (SSc) and primary biliary cholangitis (PBC) with a focus on their co-occurrence as a clinically relevant overlap syndrome. This narrative review summarizes preclinical and clinical studies addressing SSc-PBC overlap.
Recent Findings: Genomic studies highlight shared susceptibility loci between SSc and PBC.