Mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH (sometimes GPD2; gene symbol GPD2))

Mitochondrial glycerol-3-phosphate dehydrogenase is a flavoprotein enzyme (EC 1.1.5.3; gene symbol GPD2) anchored to the outer leaflet of the mitochondrial inner membrane[1][2][7]. It oxidizes glycerol-3-phosphate to dihydroxyacetone phosphate, coupling this reaction to reduction of FAD and transfer of electrons to ubiquinone in the mitochondrial electron transport chain as part of the glycerol phosphate shuttle[1][2][3]. This shuttle facilitates the transfer of reducing equivalents from cytosolic NADH into mitochondria to regenerate NAD+ for glycolysis, supporting continuous ATP production under aerobic conditions[1][2]. mGPDH is expressed in many tissues but is especially important in metabolically active types such as muscle, brown adipose, and pancreatic beta-cells, and is linked to metabolic regulation, myoblast differentiation, and adaptation to energy demands[3][5][7]. Dysregulation or altered expression of mGPDH is implicated in metabolic diseases and cancer, making it a potential therapeutic target for metabolic modulation[6]. Experimental inhibitors have enabled studies of its role and therapeutic potential, but safety concerns remain due to its fundamental importance in cellular energy metabolism[1][3].

Other names

GPD2FAD-linked glycerol-3-phosphate dehydrogenaseGlycerolphosphate dehydrogenaseGlycerol-3-phosphate:quinone oxidoreductasesn-glycerol-3-phosphate dehydrogenase (mitochondrial)Calcium-responsive mitochondrial glycerol-3-phosphate dehydrogenase

Inhibitors block the enzyme’s ability to oxidize glycerol-3-phosphate and transfer electrons to the mitochondrial electron transport chain, disrupting the glycerol phosphate shuttle and affecting NAD+ regeneration and energy production