Pyruvate dehydrogenase phosphatase regulatory subunit (PDPR)

Pyruvate dehydrogenase phosphatase regulatory subunit (PDPR) is the regulatory subunit of the mitochondrial pyruvate dehydrogenase phosphatase (PDP) complex, which dephosphorylates and activates the pyruvate dehydrogenase (PDH) complex[1][2][3][4]. PDPR is a flavoprotein that modulates the catalytic activity of PDP1 by decreasing its sensitivity to magnesium ions, a regulation that can be reversed by the polyamine spermine[1][3]. PDPR thereby plays a critical role in controlling the entry of glycolytic carbon into the tricarboxylic acid (TCA) cycle and fatty acid synthesis, linking the regulation of glucose metabolism to mitochondrial energy production[1][2][3][4]. PDPR gene variants have been implicated in rare familial phenotypes of limb-girdle muscular dystrophy and papillary thyroid cancer, where loss-of-function leads to metabolic dysregulation and may contribute to tumorigenesis[3][4]. While its precise mechanism in disease remains under investigation, available data support a possible tumor suppressor function for PDPR in glucose metabolism–dependent tissues[4]. PDPR is not currently considered a therapeutic target, and no drugs are known to modulate its function directly[3][4]. Key attributes: - FAD-containing mitochondrial regulatory protein[1][3] - Controls the reactivation of PDH by enabling PDP to dephosphorylate E1α subunit[2][4] - Regulates carbohydrate oxidation and mitochondrial energy flux[1][3] - Loss associated with enhanced phosphorylation of PDH, impaired mitochondrial function, and increased aerobic glycolysis in tumor cells[4]

Other names

PDPrPDP3KIAA1990pyruvate dehydrogenase phosphatase regulatory subunit, mitochondrial