Identification of the ATP Transporter of Rat Liver Rough Endoplasmic Reticulum via Photoaffinity Labeling and Partial Purification

Kim, Seung Hyun; Shin, Sue; Park, Jong‐Sang

doi:10.1021/bi950485h

Cited by 12 publications

(13 citation statements)

References 27 publications

(30 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One candidate ATP importer associates with ER membranes [166]. Confirming this finding, partial purification showed that an ADP/ATP antiporter of 56 kDa mediates ATP import into the ER in rat liver [167, 168], but it is not known to which ER microdomain these candidate transport proteins are localized. Thus, like calcium, ATP production in mitochondria and its consumption in the ER may influence mitochondrial activity or proximity.…”

Section: Role Of Atp For the Er-mitochondria Interaction And The Mammentioning

confidence: 99%

Oxidative protein folding in the endoplasmic reticulum: Tight links to the mitochondria-associated membrane (MAM)

Simmen

Lynes

Gesson

et al. 2010

Biochimica et Biophysica Acta (BBA) - Biomembranes

183

150

View full text Add to dashboard Cite

The production of secretory proteins at the ER (endoplasmic reticulum) depends on a ready supply of energy and metabolites as well as the close monitoring of the chemical conditions that favor oxidative protein folding. ER oxidoreductases and chaperones fold nascent proteins into their export-competent three-dimensional structure. Interference with these protein folding enzymes leads to the accumulation of unfolded proteins within the ER lumen, causing an acute organellar stress that triggers the UPR (unfolded protein response). The UPR increases the transcription of ER chaperones commensurate with the load of newly synthesized proteins and can protect the cell from ER stress. Persistant stress, however, can force the UPR to commit cells to undergo apoptotic cell death, which requires the emptying of ER calcium stores. Conversely, a continuous ebb and flow of calcium occurs between the ER and mitochondria during resting conditions on a domain of the ER that forms close contacts with mitochondria, the MAM (mitochondria-associated membrane). On the MAM, ER folding chaperones such as calnexin and calreticulin and oxidoreductases such as ERp44, ERp57 and Ero1α regulate calcium flux from the ER through reversible, calcium and redox-dependent interactions with IP3Rs (inositol 1,4,5-trisphophate receptors) and with SERCAs (sarcoplasmic/endoplasmic reticulum calcium ATPases). During apoptosis progression and depending on the identity of the ER chaperone and oxidoreductase, these interactions increase or decrease, suggesting that the extent of MAM targeting of ER chaperones and oxidoreductases could shift the readout of ER-mitochondria calcium exchange from housekeeping to apoptotic. However, little is known about the cytosolic factors that mediate the on/off interactions between ER chaperones and oxidoreductases with ER calcium channels and pumps. One candidate regulator is the multi-functional molecule PACS-2 (phosphofurin acidic cluster sorting protein-2). Recent studies suggest that PACS-2 mediates localization of a mobile pool of calnexin to the MAM in addition to regulating homeostatic ER calcium signaling as well as MAM integrity. Together, these findings suggest cytosolic, membrane and lumenal proteins combine to form a two-way switch that determines the rate of protein secretion by providing ions and metabolites and that appears to participate in the pro-apoptotic ER-mitochondria calcium transfer.

show abstract

Section: Role Of Atp For the Er-mitochondria Interaction And The Mammentioning

confidence: 99%

Oxidative protein folding in the endoplasmic reticulum: Tight links to the mitochondria-associated membrane (MAM)

Simmen

Lynes

Gesson

et al. 2010

Biochimica et Biophysica Acta (BBA) - Biomembranes

183

150

View full text Add to dashboard Cite

show abstract

“…It is suggested that there is an ATP transporter on the microsomal membrane that draws ATP into the lumen (Clairmont et al, 1992;Kim et al, 1996). ATP uptake into microsomes is saturable with a K m of 3 to 4 M and a V max of 3 to 7 pmol ⅐ min Ϫ1 ⅐ mg protein Ϫ1 (Clairmont et al, 1992).…”

Section: Release Of Atp From Rlm By Brij-58 and Alamethicin Treatmentmentioning

confidence: 99%

ATP Serves as an Endogenous Inhibitor of UDP-Glucuronosyltransferase (UGT): A New Insight into the Latency of UGT

Ishii

Nishimura

et al. 2012

Drug Metab Dispos

View full text Add to dashboard Cite

ABSTRACT:We have suggested that adenine-related compounds are allosteric inhibitors of UGT in rat liver microsomes (RLM) treated with detergent. To clarify whether the same occurs with a pore-forming peptide, alamethicin, the effects of adenine-related compounds on 4-metylumbelliferone (4-MU) glucuronidation were examined using RLM and human liver microsomes (HLM). ATP inhibited 4-MU glucuronidation when polyoxyethylene cetyl alcohol ether (Brij-58)-treated RLM were used (IC 50 ‫؍‬ approximately 70 M). However, alamethicin-treated RLM exhibited a lower susceptibility (IC 50 ‫؍‬ approximately 460 M) than Brij-58-treated RLM. A similar phenomenon was observed when pooled HLM were used. Then, the endogenous ATP content of RLM was determined in the presence and absence of alamethicin or detergent, and although no ATP remained in the microsomal pellets after Brij-58 treatment, more than half of the microsomal ATP remained even after treatment with alamethicin. Furthermore, the V max in the absence of an adenine-related compound was approximately three times higher in Brij-58-treated than in alamethicin-treated RLM. The difference in the inhibitory potency observed was due to the difference in remaining endogenous ATP and the accessibility of exogenous ATP to the luminal side of the endoplasmic reticulum (ER), where the active site of UDP-glucuronosyltransferase (UGT) is located. Gefitinib (Iressa), a protein tyrosine kinase inhibitor, markedly inhibited human UGT1A9 activity. It is interesting to note that AMP antagonized Gefitinib-provoked inhibition of UGT1A9, and ATP exhibited an additive inhibitory effect at a lower concentration. Therefore, Gefitinib inhibits UGT1A9 at the common ATP-binding site shared with ATP and AMP. Releasing adenine nucleotide from the ER is suggested to be one of the mechanisms that explain the "latency" of UGT.

show abstract

“…The ATP transporter from S. cerevisiae has been purified and cloned (69), whereas that from rat liver has been reconstituted, partially purified (90), and identified through use of a photoaffinity label as a 56-kDa protein (70). The ATP transporter from the endoplasmic reticulum of S. cerevisiae was characterized as a 68-kDa protein by combining fractionation studies with reconstitution of proteoliposomes.…”

Section: Transport Of Atp and Nucleotide Sugars Into The Endoplasmic mentioning

confidence: 99%

Transporters of Nucleotide Sugars, Atp, and Nucleotide Sulfate in the Endoplasmic Reticulum and Golgi Apparatus

Hirschberg

Robbins²,

Abeijón³

1998

Annu. Rev. Biochem.

343

306

View full text Add to dashboard Cite

The lumens of the endoplasmic reticulum and Golgi apparatus are the subcellular sites where glycosylation, sulfation, and phosphorylation of secretory and membrane-bound proteins, proteoglycans, and lipids occur. Nucleotide sugars, nucleotide sulfate, and ATP are substrates for these reactions. ATP is also used as an energy source in the lumen of the endoplasmic reticulum during protein folding and degradation. The above nucleotide derivatives and ATP must first be translocated across the membrane of the endoplasmic reticulum and/or Golgi apparatus before they can serve as substrates in the above lumenal reactions. Translocation of the above solutes is mediated for highly specific transporters, which are antiporters with the corresponding nucleoside monophosphates as shown by biochemical and genetic approaches. Mutants in mammals, yeast, and protozoa showed that a defect in a specific translocator activity results in selective impairments of the above posttranslational modifications, including loss of virulence of pathogenic protozoa. Several of these transporters have been purified and cloned. Experiments with yeast and mammalian cells demonstrate that these transporters play a regulatory role in the above reactions. Future studies will address the structure of the above proteins, how they are targeted to different organelles, 49 0066-4154/98/0701-0049$08.00 Annu. Rev. Biochem. 1998.67:49-69

show abstract

Identification of the ATP Transporter of Rat Liver Rough Endoplasmic Reticulum via Photoaffinity Labeling and Partial Purification

Cited by 12 publications

References 27 publications

Oxidative protein folding in the endoplasmic reticulum: Tight links to the mitochondria-associated membrane (MAM)

Oxidative protein folding in the endoplasmic reticulum: Tight links to the mitochondria-associated membrane (MAM)

ATP Serves as an Endogenous Inhibitor of UDP-Glucuronosyltransferase (UGT): A New Insight into the Latency of UGT

Transporters of Nucleotide Sugars, Atp, and Nucleotide Sulfate in the Endoplasmic Reticulum and Golgi Apparatus

Contact Info

Product

Resources

About