Friedreich ataxia: III. Mitochondrial malic enzyme deficiency

Polarographic assays of oxidative phosphorylation in muscle mitochondria indicated abnormal pyruvate-malate metabolism in Friedreich ataxia (FA). Pursuing this clue, more specific assays were performed. Mitochondrial malic enzyme (ME_m; malate: NADP oxidoreductase) specific activity was 10% of controls in fibroblasts from eight FA patients (p < 0.0001). Cytosolic malic enzyme was modestly increased in FA fibroblasts. Mitochondrial and cytosolic malate dehydrogenase and aspartate aminotransferase, and inalate transport on the dicarboxylate and a-ketoglutarate carriers were normal in fibroblasts or leukocytes. MEm activity is normally highest in the nervous system and heart and is important in regulating carbohydrate metabolism. MEm deficiency could cause FA; further studies are required to substantiate this hypothesis.