Eukaryotic cells appear ubiquitously to express two forms of NAD⁺-dependent malate dehydrogenase ( L-malate : NAD⁺ oxidoreductase, MDH, EC 1.1.1.37), which occur exclusively in the cytosol (cMDH) and in the mitochondria (mMDH) respectively (Banaszak and Bradshaw 1975). The independent genetic origins of these MDH isoenzymes have been confirmed by the discovery of rare variants of mMDH that are inherited in a Mendelian fashion without corresponding changes in the cytoplasmic form (Davidson and Cortner 1967). The gene determining mMDH has been mapped to chromosome 7, and that determining the cytoplasmic isoenzyme to chromosome 2, in man (McKusick and Ruddle 1977, Moss 1982). Both isoenzymes of MDH are synthesized in the cytoplasm, where cMDH remains after acetylation of the N-terminal residue. mMDH is synthesized as a higher molecular mass precursor (Aziz et al. 1981, Mihara et al. 1982), due to an N-terminal extension (or “transit peptide”) of 24 amino acids in mammals (Grant et al. 1986, Joh et al. 1987a) and of 27 amino acids in higher plants (Gietl et al. 1990), and is subsequently imported to the mitochondrial matrix (Chien and Freeman 1984). The translocation sequence is essential for this process and is proteolytically cleaved during the mitochondrial import of the enzyme (Chu et al. 1987).