Mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH) (mGPDH)

Mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH), encoded by the GPD2 gene, is a key enzyme located on the outer face of the inner mitochondrial membrane (UniProt P43304). It functions as a component of the glycerol-3-phosphate shuttle, one of the two primary redox shuttles that transfer reducing equivalents from cytosolic NADH to the mitochondrial electron transport chain (Mracek et al., 2013). By maintaining the cytosolic NAD+/NADH ratio, mGPDH supports continued glycolytic flux and regulates metabolic pathways such as gluconeogenesis and lipogenesis. Research indicates that mGPDH is a primary molecular target for the antidiabetic drug metformin, which non-competitively inhibits the enzyme to suppress glucose production in the liver (Madiraju et al., 2014). Additionally, mGPDH is frequently upregulated in various malignancies, such as prostate and thyroid cancers, where it supports the metabolic demands of rapidly proliferating cells (Langston et al., 2016). Targeting mGPDH offers a therapeutic strategy for metabolic disorders and oncology by modulating cellular redox states and energy metabolism.

Other names

Glycerol-3-phosphate dehydrogenase 2GPD2GPD-MMitochondrial glycerophosphate dehydrogenaseGlycerol-3-phosphate dehydrogenase (mitochondrial)

Inhibition of mGPDH activity disrupts the glycerol-3-phosphate shuttle, leading to an increase in the cytosolic NADH/NAD+ ratio, which subsequently inhibits hepatic gluconeogenesis from lactate and glycerol (Madiraju et al., 2014).