A putative precursor of rat liver mitochondrial malate dehydrogenase

Aziz, Laurel E.; Chien, Sin-Ming; Patel, Hasmukh V.; Freeman, Karl B.

doi:10.1016/0014-5793(81)80487-5

Cited by 28 publications

(15 citation statements)

References 23 publications

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“…The length of the mMDH extra sequence, however, fits into the normal range observed in mitochondrial precursor proteins. A putative precursor for rat liver and bovine heart mMDH has been recently reported (2). The size of the extra sequence is 1,500 to 2,000 daltons, which is somewhat smaller than the extension of the watermelon mMDH.…”

Section: Discussionmentioning

confidence: 98%

Organelle-Bound Malate Dehydrogenase Isoenzymes Are Synthesized as Higher Molecular Weight Precursors

Gietl

Hock²

1982

Plant Physiol.

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Biosynthesis of malate dehydrogenase isoenzymes was studied in cotyledons of watermelons (Citrudlus vulgaris Schrad., var. Stone Mountain). The glyoxysomal and mitochondrial isoenzymes are synthesized as higher molecular weight precursors which can be immunoprecipitated by monospecific antibodies from the products of in vitro translation in reticulocyte lysates programed with cotyledonary mRNA and with the same size from enzyme extracts of pulse-labeled cotyledons. During translocation from the cytosol into the organelles, processing takes place. An 8 kilodalton extra sequence is cleaved from the glyoxysomal precursor and a 3.3 kilodalton extra sequence from the mitochondrial precursor producing the native subunits of 33 and 38 kilodaltons, respectively. The data support a posttranslational translocation of the organelle-destined malate dehydrogenase isoenzymes. The in vitro translation of the cytosolic malate dehydrogenase I yields a product which has the same molecular weight as the subunit of the native isoenzyme (39.5 kilodaltons).distinguished by electrophoretic or serological techniques. Earlier studies on the in vitro synthesis of gMDH by a wheat germ system by our group (26) had shown that this isoenzyme is made as a higher mol wt polypeptide compared with the subunit of gMDH isolated from watermelon cotyledons thereby suggesting the need for processing during the importation into the glyoxysomes. The results were confirmed subsequently by Riezman et al. (20) for cucumber cotyledons.We now present a comparative study on the in vitro synthesis of gMDH, mMDH, and cMDH I using the heterologous reticulocyte system. Our results indicate that mMDH also is synthesized as a larger in vitro product3 in contrast to the cytosolic isoenzyme.Pulse labeling experiments provided evidence that the higher mol wt MDH polypeptide precursors were also detectable under in vivo conditions. The posttranslational implications for the role of such precursors in directing transport into glyoxysomes and mitochondria are discussed. MATERIALS AND METHODSThe development of cell organelles requires the import of proteins which are synthesized on cytoplasmic ribosomes. The translocation from the site of synthesis to the site of function involves a highly specific recognition mechanism by the organelle envelope which only accepts the organelle-destined proteins for segregation within the organelle.The use of isoenzyme system for translocation studies requires that individual isoenzymes be located in different organelles within the same cell. Differences in these proteins or their precursors should be related, at least in part, to the pattern of distribution. Only a very few isoenzyme systems have been employed in this way, e.g. the aspartate aminotransferase (17) and the malate dehydrogenase (19) from rat liver where the mitochondrial and the cytosolic isoenzymes were compared. In vitro transport studies with purified isoenzymes revealed that the high selectivity of the isoenzyme sequestration by the mitochondria could be relate...

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Section: Discussionmentioning

confidence: 98%

Organelle-Bound Malate Dehydrogenase Isoenzymes Are Synthesized as Higher Molecular Weight Precursors

Gietl

Hock²

1982

Plant Physiol.

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“…In eukaryotic cells, two MDH isozymes are encoded by nuclear genes and are synthesized in the cytoplasm. Cytosolic MDH (MDH1) remains in the cytosol after synthesis whereas mitochondrial MDH (MDH2) is translocated into the mitochondrial matrix facilitated by an aminoterminal polypeptide signal [Aziz et al, 1981;Grant et al, 1987;Hartmann et al, 1993].…”

Section: Nadmentioning

confidence: 99%

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

Liew

Ngai

et al. 2004

J of Cellular Biochemistry

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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.

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“…sMDH remains in the cytosol after synthesis whereas mMDH is translocated into the mitochondrial matrix, a process that may be facilitated by the presence of a leader sequence at the amino terminus of the polypeptide chain (4). The compartmentalization of sMDH and mMDH has physiological significance; sMDH functions in the malate-aspartate shuttle whereas mMDH is a.key enzyme in the same shuttle and in the citric acid cycle.…”

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confidence: 99%

Amino acid sequence homology among the 2-hydroxy acid dehydrogenases: mitochondrial and cytoplasmic malate dehydrogenases form a homologous system with lactate dehydrogenase.

Birktoft¹,

Fernley²,

Bradshaw³

et al. 1982

Proc. Natl. Acad. Sci. U.S.A.

123

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The amino acid sequence of porcine heart mitochondrial malate dehydrogenase (mMDH; L-malate:NAD+ oxidoreductase, EC 1.1.1.37) has been compared with the sequences of six different lactate dehydrogenases (LDH; Llactate:NAD' oxidoreductase, EC 1.1.1.27) and with the "x-ray" sequence of cytoplasmic.malate dehydrogenase (sMDH). The main points are that (i) all three enzymes are homologous; (ii) invariant residues in the catalytic center of these enzymes include a histidine and an internally located aspartate that function as a proton relay system; (iii) numerous residues important to coenzyme binding are conserved, including several glycines and charged residues; and (iv) amino acid side chains present in the subunit interface common to the MDHs and LDHs appear to be better conserved than those in the protein interior. It is concluded that LDH, sMDH, and mMDH are derived from a common ancestral gene and probably have similar catalytic mechanisms.

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A putative precursor of rat liver mitochondrial malate dehydrogenase

Cited by 28 publications

References 23 publications

Organelle-Bound Malate Dehydrogenase Isoenzymes Are Synthesized as Higher Molecular Weight Precursors

Organelle-Bound Malate Dehydrogenase Isoenzymes Are Synthesized as Higher Molecular Weight Precursors

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

Amino acid sequence homology among the 2-hydroxy acid dehydrogenases: mitochondrial and cytoplasmic malate dehydrogenases form a homologous system with lactate dehydrogenase.

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