Bovine cardiac mitochondrial ADP/ATP-carrier: Two distinct mRNAs and an unusually short 3′-noncoding sequence

Rasmussen, Ulla; Wohlrab, Hartmut

doi:10.1016/s0006-291x(86)80574-5

Cited by 26 publications

(14 citation statements)

References 36 publications

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“…The skeletal muscle ANT gene appears to be expressed in a wide variety of tissues. Our coding region and the 3' noncoding region oligonucleotide probes hybridized to 1.43-kb mRNAs from human heart, kidney, skeletal muscle, and HeLa cells; our skeletal muscle and liver cDNA sequences were almost identical; and our skeletal muscle cDNA sequence is highly homologous to both the beef heart amino acid sequence (17) and the partial beef heart ANT cDNA sequence encoding a 91-amino acid peptide (12). The similarity between the human skeletal muscle ANT and the bovine heart ANT cDNAs is further supported by the close proximity of one of 'two ATTAAA poly(A)-addition signals four nucleotides downstream from the termination codon.…”

Section: Discussionmentioning

confidence: 87%

“…We have compared our sequence 11 with a recently published cDNA sequence for a human fibroblast ANT cognate (11) and with a partial cDNA sequence of the bovine heart ANT (12). These data, together with mRNA analysis, demonstrate that there are two distinct ANTs that diverged about 275 million years before present (MYBP) and that the skeletal muscle ANT is expressed in heart, kidney, liver, skeletal muscle, and HeLa cells.…”

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confidence: 97%

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cDNA sequence of a human skeletal muscle ADP/ATP translocator: lack of a leader peptide, divergence from a fibroblast translocator cDNA, and coevolution with mitochondrial DNA genes.

Neckelmann

Wade

et al. 1987

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

180

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We have characterized a 1400-nucleotide cDNA for the human skeletal muscle ADP/ATP translocator. The deduced amino acid sequence is 94% homologous to the beef heart ADP/ATP translocator protein and contains only a single additional amino-terminal methionine. This implies that the human translocator lacks an amino-terminal targeting peptide, a conclusion substantiated by measuring the molecular weight of the protein synthesized in vitro. A 1400-nucleotide transcript encoding the skeletal muscle translocator was detected on blots oftotal RNA from human heart, kidney, skeletal muscle, and HeLa cells by hybridization with oligonucleotide probes homologous to the coding region and 3' noncoding region of the cDNA. However, the level of this mRNA varied substantially among tissues. Comparison of our skeletal muscle translocator sequence with that of a recently published human fibroblast translocator cognate revealed that the two proteins are 88% identical and diverged about 275 million years ago. Hence, tissues vary both in the level of expression of individual translocator genes and in differential expression of cognate translocator genes. Comparison of the base substitution rates of the ADP/ATP translocator and the oxidative phosphorylation genes encoded by mitochondrial DNA revealed that the mitochondrial DNA genes fix 10 times more synonymous substitutions and 12 times more replacement substitutions; yet, these nuclear and cytoplasmic respiration genes experience comparable evolutionary constraints. This suggests that the mitochondrial DNA genes are highly prone to deleterious mutations.The ADP/ATP translocator, or adenine nucleotide translocator (ANT), is the most abundant mitochondrial protein (1). In its functional state it forms a dimer consisting of two identical 30-kDa subunits embedded asymmetrically in the inner mitochondrial membrane (2). The dimer forms a gated pore through which ADP is moved across the inner membrane into the mitochondrial matrix and ATP is moved from the matrix into the cytoplasm (2).Mitochondrial energy production varies greatly in importance between human tissues (3). Because the ANT determines the rate of ADP/ATP flux between the mitochondrion and the cytosol, the ANT would be a logical site for regulating cellular dependence on oxidative energy metabolism. Such regulation could be accomplished by producing varying amounts of the ANT or by elaborating tissue-specific ANT isoforms with different kinetic properties. Although Neurospora crassa has only one ANT gene (4), antigenic and electrophoretic mobility differences among bovine heart, kidney, and liver ANTs (5, 6) suggest that mammals may have multiple ANT genes that are expressed in a tissuespecific manner. Tissue-specific expression of functionally similar genes encoding proteins involved in oxidative phosphorylation (Ox/Phos) has been reported for the bovine ATP synthase proteolipid (7).The ANT and most other Ox/Phos genes are encoded in the nucleus, but 13 essential Ox/Phos polypeptides are encoded in the maternally inh...

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Section: Discussionmentioning

confidence: 87%

mentioning

confidence: 97%

cDNA sequence of a human skeletal muscle ADP/ATP translocator: lack of a leader peptide, divergence from a fibroblast translocator cDNA, and coevolution with mitochondrial DNA genes.

Neckelmann

Wade

et al. 1987

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

180

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“…Nucleotide sequence information of Y-ends of all known genes of nuclear-encoded mitochondrial proteins has been used for the analysis: rat cytochrome c [11], (R cyt c); bovine cytochrome P-450 (SSC) [12], (B cytP450); bovine adrenodoxin [13], (B Adrdox); rat ornithine aminotransferase [14], (R OAT); porcine mitochondrial a:~partate aminotransferase [15], (P mAspAT); bovine mitochondrial ATP synthase proteolipid [16], (B P1ATPas, B P2ATPas); human aldehyde dehydrogenase 2 [17], (H ALDH2); rat carbamyl synthetase 1 [18], (R cps); human F1-ATPase (subunit) [19], (H ATPsyn); human cytochrome P-450 (SSC) [20], (H cytP450); chicken 5-aminolevulinate synthase [21], (C 5'ala); bovine ADP/ATP carrier [22], (B ADPATPc); human ornithine aminotransferase [23], (H OAT); mouse asparta~e aminotransferase [24], (M rnAspAT); rat serine; pyruvate aminotransferase [25], (R srpyatase); bovine ATP synthase; precursors for oligomycin sensitivity conferring protein, factor 6 and adenosine° triphosphatase inhibitor protein [26], (B OSCP, B F6, B ATPasin); rat aspartate aminotransferase [27], (R mAspAT); human medium-chain acyl-CoA dehydrogenase [28], (H acylCod); human 5-aminolevulinate synthase [29], (H 5'ala); human subunit 4 of cytochrome oxidase [30], (H coxlV); human ADP/ATP carrier [31], (H ADPATPc); rat EIcz subunit of branched chain ~z-ketoacid dehydrogenase [32], (R E~ BCKD); porcine and human lipoamide dehydrogenase [33], (H LPdehyd, P LPdehyd); bovine adrenodoxin reductase [34], (B Adrdred); bovine steroid l lfl-hydroxylase (p450 ell) [35]. (B cyt45011); rat ornithine carbamoyltransferase [36], (R oct); human pyruvate dehydrogenase EI~ subunit [37], (H PyrDhE1); bovine mitochondrial adenylate kinase 2 [38], (B AK2A, B AK2B); bovine mitochondrial carrier protein [39], (B mtPcP); rat mitochondrial 3-oxoacyl-CoA thiolase [40], (R 3oxCoth); human liver glutamate dehydrogenase [41], (H GDH); rat heart and liver subunit Via of cytochrome oxidase …”

Section: Resultsmentioning

confidence: 99%

Analysis of the polyadenylation consensus sequence context in the genes of nuclear encoded mitochondrial proteins

Juretić

Theus

1991

FEBS Letters

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A compilation of the pre-mRNA ends of the genes of nuclear encoded mitochondrial proteins resulted in a consensus sequence of the type (T/A)NTTNNNNNTTTNAATAAA. Nucleotide positions +8, +13. +14, +16 and +17 downstream of the AATAAA sequence show also a predominance of nucleotide T. This consensus sequence suggests the importance of the immediate surroundings of the cannonical polyadenylation signal sequence AATAAA on the efficiency of" the cleavage and polyadenylation of this specific group of pre-mRNAs.Nuclear encoded mitochondrial protein; RNA processing

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“…This would imply a complexity of the genes for the ADP/ATP translocase even greater than so far suspected. In previous work (29), two distinct mRNAs with sizes of 1200 and 1500 nt were detected in bovine tissues (heart, kidney, liver, and uterus) by using ADP/ATP translocase cDNA clones isolated from a bovine heart library as probes. It was postulated that these two mRNAs differ in the lengths of their 5' untranslated region.…”

Section: Discussionmentioning

confidence: 99%

Two distinct genes for ADP/ATP translocase are expressed at the mRNA level in adult human liver.

Houldsworth

Attardi

1988

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

124

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Several The ADP/ATP translocase is an integral protein of the inner mitochondrial membrane that carries out the exchange between the extramitochondrial and intramitochondrial ADP and ATP, linking the processes of ATP production to those of ATP utilization (1). This protein can thus exert a control on the rate of oxidative phosphorylation, as well as on the rates of the energy-consuming processes. Because of its central role in cellular energy metabolism, the ADP/ATP translocase is likely to be a highly regulated protein to fit the varying demands of the cell in relationship to functional, developmental, and tissue-specific factors. Indeed, evidence coming from an analysis of the immunological reactivity of the translocator protein extracted from different tissues (2, 3) and of the tissue specificity of anti-translocase autoantibodies found in some heart (4) and liver diseases (5) has strongly suggested the existence of multiple isoforms of this protein. These findings fit in well with the emerging concept of a developmental and tissue-specific control of the apparatus of oxidative phosphorylation. The isolation from a human fibroblast cDNA library of a clone for an ADP/ATP translocase that is growthregulated has recently been reported (6). In this paper, we report on the isolation and structural characterization of cDNAs for the ADP/ATP translocase from an adult human liver cDNA library. Evidence is presented that two different genes for this protein, one of which may correspond to the gene identified in human fibroblasts (6)

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Bovine cardiac mitochondrial ADP/ATP-carrier: Two distinct mRNAs and an unusually short 3′-noncoding sequence

Cited by 26 publications

References 36 publications

cDNA sequence of a human skeletal muscle ADP/ATP translocator: lack of a leader peptide, divergence from a fibroblast translocator cDNA, and coevolution with mitochondrial DNA genes.

cDNA sequence of a human skeletal muscle ADP/ATP translocator: lack of a leader peptide, divergence from a fibroblast translocator cDNA, and coevolution with mitochondrial DNA genes.

Analysis of the polyadenylation consensus sequence context in the genes of nuclear encoded mitochondrial proteins

Two distinct genes for ADP/ATP translocase are expressed at the mRNA level in adult human liver.

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