Developmental regulation and cellular distribution of human cytosolic malate dehydrogenase (MDH1)

Human cyotsolic malate dehydrogenase (MDH1) is important in transporting NADH equivalents across the mitochondrial membrane, controlling tricarboxylic acid (TCA) cycle pool size and providing contractile function. Cellular localization studies indicate that MDH1 mRNA expression has a strong tissue-specific distribution, being expressed primarily in cardiac and skeletal muscle and in the brain, at intermediate levels in the spleen, kidney, intestine, liver, and testes and at low levels in lung and bone marrow. The observed MDH1 localizations reflect the role of NADH in the support of a variety of functions in different organs. These functions are primarily related to aerobic energy production for muscle contraction, neuronal signal transmission, absorption/resorption functions, collagen-supporting functions, phagocytosis of dead cells, and processes related to gas exchange and cell division. During neonatal development, MDH1 is expressed in human embryonic heart as early as the 3rd month and then is over-expressed from the 5th month until the birth. The expression of MDH1 is maintained in the adult heart but is not present in levels as high as in the fetus. Finally, over-expression of MDH1 is found in left ventricular cardiac muscle of dilated cardiomyopathy (DCM) patients when contrasted to the diseased non-DCM and normal heart muscle by in situ hybridization and Western blot. These observations are compatible with the activation of glucose oxidation in relatively hypoxic environments of fetal and hypertrophied myocardium.