The ADP/ATP Carrier in Mitochondrial Membranes

Klingenberg, Martin

doi:10.1007/978-1-4684-4604-3_15

Cited by 73 publications

(25 citation statements)

References 93 publications

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“…3 shows that ATP, GTP, and UTP are all substrates for the chromaffin granule nucleotide transporter. This lack of specificity for nucleotides was reported previously for transport into intact chromaffin granules (18) and distinguishes the chromaffin granule system from the ATP/ADP exchanger of mitochondria, which is highly selective for ATP and ADP and will not transport other nucleotides (25).…”

Section: Active Atp Transport Into Chromaffin Granule Ghosts-supporting

confidence: 52%

“…Since DIDS does not significantly inhibit the formation of the pH gradient (⌬pH ϭ 0.89 in the presence of 20 M DIDS and ⌬pH ϭ 0.96 in the absence of DIDS; DIDS inhibits ATP transport approximately 50% at this concentration), we conclude that it inhibits ATP transport preferentially as compared to the H ϩ -ATPase. Atractyloside Inhibition of ATP Transport-It has been reported that atractyloside, an inhibitor of the mitochondrial ATP/ADP exchanger (25), inhibits nucleotide uptake by intact granules (17). We find that the effect of atractyloside depends on the relative concentrations of ATP and Mg A, chromaffin granule ghosts were incubated in buffer containing 0 -150 mM KCl, each osmotically balanced to 300 mosm with sucrose, 10 mM HEPES, pH 7, 5 mM MgATP for 10 min at 37°C.…”

Section: Atp Associated With Granule Ghosts Is Releasable-mentioning

confidence: 76%

“…Furthermore, GTP and UTP are also transported into chromaffin granule ghosts; these nucleotides are not substrates for the mitochondrial exchanger (25). However, both transporters can be inhibited by atractyloside, although the chromaffin granule system is only very weakly inhibited.…”

Section: Atp Associated With Granule Ghosts Is Releasable-mentioning

confidence: 99%

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Characterization of ATP Transport into Chromaffin Granule Ghosts

Bankston¹,

Guidotti²

1996

Journal of Biological Chemistry

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ATP is an excitatory neurotransmitter that is stored and cosecreted with catecholamines from cells of the adrenal medulla. While the transport of catecholamines into chromaffin granule ghosts has been extensively characterized, there is little information on the mechanism of ATP transport into these structures. Here we show that ATP transport is driven by the electrical component of the electrochemical proton gradient created by the chromaffin granule membrane H

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Section: Active Atp Transport Into Chromaffin Granule Ghosts-supporting

confidence: 52%

Section: Atp Associated With Granule Ghosts Is Releasable-mentioning

confidence: 76%

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Characterization of ATP Transport into Chromaffin Granule Ghosts

Bankston¹,

Guidotti²

1996

Journal of Biological Chemistry

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“…The AAC has been instrumental in understanding certain principles of transport mechanism, such as the "single binding gated pore mechanism" (2-4) and the "induced transition fit" (5, 6) of transport catalysis. The drastic conformation changes linked to the transport are well documented (7,8). Based on its sequence and topological studies, it is generally assumed that the AAC has six transmembrane helices, with three repeat domains containing two helices each.…”

Section: The Adp/atp Carrier (Aac)mentioning

confidence: 99%

Expression of the Mitochondrial ADP/ATP Carrier inEscherichia coli

Heimpel¹,

Basset²,

Odoy³

et al. 2001

Journal of Biological Chemistry

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Previously, the role of residues in the ADP/ATP carrier (AAC) from Saccharomyces cerevisiae has been studied by mutagenesis, but the dependence of mitochondrial biogenesis on functional AAC impedes segregation of the mutational effects on transport and biogenesis. Unlike other mitochondrial carriers, expression of the AAC from yeast or mammalians in Escherichia coli encountered difficulties because of disparate codon usage. Here we introduce the AAC from Neurospora crassa in E. coli, where it is accumulated in inclusion bodies and establish the reconstitution conditions. AAC expressed with heat shock vector gave higher activity than with pET-3a. Transport activity was absolutely dependent on cardiolipin. The 10 single mutations of intrahelical positive residues and of the matrix repeat (؉X؉) motif resulted in lower activity, except of R245A. R143A had decreased sensitivity toward carboxyatractylate. The ATP-linked exchange is generally more affected than ADP exchange. This reflects a charge network that propagates positive charge defects to ATP 4؊ more strongly than to ADP 3؊ transport. Comparison to the homologous mutants of yeast AAC2 permits attribution of the roles of these residues more to ADP/ATP transport or to AAC import into mitochondria. The ADP/ATP carrier (AAC)1 is involved in the last step of the oxidative phosphorylation system by delivering ATP into the cytosol. Its slow intrinsic turnover is a result of unusually large and highly charged substrates; it is the most strongly expressed member of the mitochondrial carrier family (1). The AAC has been instrumental in understanding certain principles of transport mechanism, such as the "single binding gated pore mechanism" (2-4) and the "induced transition fit" (5, 6) of transport catalysis. The drastic conformation changes linked to the transport are well documented (7,8). Based on its sequence and topological studies, it is generally assumed that the AAC has six transmembrane helices, with three repeat domains containing two helices each. However, very little is known about the three-dimensional structure of the AAC, as is the situation with all mitochondrial solute transporters.We have approached the structure-function relationship problem of the AAC in recent years by mutating residues within the AAC2 from Saccharomyces cerevisiae. Most mutations involved neutralizing charged residues and the effects on various functions were determined (9 -11). A beneficial spin-off from the yeast system was the occurrence of spontaneous revertants by second-site mutations (12)(13)(14). A disadvantage of the yeast expression system is the dependence on mitochondrial growth and biogenesis on the transport performance of AAC. The level of AAC expression varied widely among the mutants and could be drastically suppressed. Therefore, in several mutants that lacked AAC protein, the functional effect could not be accurately determined. Further, it could not be clearly deduced whether the mutated residue was involved primarily in the incorporation or in the transport fun...

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“…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.…”

mentioning

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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The ADP/ATP Carrier in Mitochondrial Membranes

Cited by 73 publications

References 93 publications

Characterization of ATP Transport into Chromaffin Granule Ghosts

Characterization of ATP Transport into Chromaffin Granule Ghosts

Expression of the Mitochondrial ADP/ATP Carrier inEscherichia coli

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

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