Home LiteratureArticle Details
PMID: 1373486 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Isolation of the mitochondrial benzodiazepine receptor: association with the voltage-dependent anion channel and the adenine nucleotide carrier.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 89 ·No. 8 ·1992-04-15 ·Pages 3170-4

McEnery MW, Snowman AM, Trifiletti RR, Snyder SH

Abstract

The mitochondrial benzodiazepine receptor (mBzR) has been solubilized with retention of reversible ligand binding, and the associated subunits were characterized. mBzR comprises immunologically distinct protein subunits of 18-, 30-, and 32-kDa. The 18-kDa protein is labeled by the isoquinoline carboxamide mBzR ligand [3H]PK14105, whereas the 30- and 32-kDa subunits are labeled by the benzodiazepine (Bz) ligands [3H]flunitrazepam and [3H]AHN-086. Selective antibodies and reagents identify the 32- and 30-kDa proteins as the voltage-dependent anion channel (VDAC) and the adenine nucleotide carrier (ADC), respectively. While isoquinoline carboxamide and Bz ligands target different subunits, they interact allosterically, as the binding of Bz and isoquinoline carboxamide ligands is mutually competitive at low nanomolar concentrations. Moreover, eosin-5-maleimide and mercuric chloride inhibit [3H]PK11195 binding to the intact receptor via sulfhydryl groups that are present in ADC. VDAC and ADC, outer and inner mitochondrial membrane channel proteins, respectively, together with the 18-kDa subunit, may comprise mBzR at functionally important transport sites at the junction of two mitochondrial membranes.

MeSH Terms
Affinity Labels/metabolism Animals Benzodiazepinones/metabolism Binding Sites Flunitrazepam/metabolism Ion Channels/metabolism Isoquinolines/metabolism Kidney/metabolism Kinetics Male Mitochondria/drug effects,metabolism Mitochondrial ADP, ATP Translocases/isolation & purification,metabolism Rats Rats, Inbred Strains Receptors, GABA-A/isolation & purification,metabolism Sulfhydryl Reagents/pharmacology Urea/pharmacology
Chemicals
Affinity Labels Benzodiazepinones Ion Channels Isoquinolines Receptors, GABA-A Sulfhydryl Reagents AHN 086 Flunitrazepam Urea Mitochondrial ADP, ATP Translocases PK 14105
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
McEnery M W
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2185.
Snowman A M
Trifiletti R R
Snyder S H
References (58)
58 references, click to expand
  1. Hormone-stimulated steroidogenesis is coupled to mitochondrial benzodiazepine receptors. Tropic hormone action on steroid biosynthesis is inhibited by flunitrazepam.
    J Biol Chem. 1991 Feb 25;266(6):3682-7 PMID: 1847384
  2. The 35 kDa DCCD-binding protein from pig heart mitochondria is the mitochondrial porin.
    Biochim Biophys Acta. 1985 Mar 14;813(2):230-42 PMID: 2578813
  3. Two subcellular locations for peripheral-type benzodiazepine acceptors in rat liver.
    Eur J Biochem. 1990 Feb 22;188(1):131-8 PMID: 2156692
  4. Dihydropyridine and peripheral type benzodiazepine binding sites: subcellular distribution and molecular size determination.
    Eur J Pharmacol. 1985 Dec 17;119(3):153-67 PMID: 2419140
  5. [3H]AHN 086 acylates peripheral benzodiazepine receptors in the rat pineal gland.
    FEBS Lett. 1989 Feb 27;244(2):263-7 PMID: 2537753
  6. Peripheral type benzodiazepine receptors.
    Annu Rev Pharmacol Toxicol. 1989;29:307-22 PMID: 2543271
  7. Molecular cloning and expression of cDNA encoding a peripheral-type benzodiazepine receptor.
    J Biol Chem. 1989 Dec 5;264(34):20415-21 PMID: 2555358
  8. Adenine nucleotide and phosphate transport systems of mitochondria. Relative location of sulfhydryl groups based on the use of the novel fluorescent probe eosin-5-maleimide.
    J Biol Chem. 1985 May 25;260(10):6288-95 PMID: 2581951
  9. The peripheral-type benzodiazepine receptor: a protein of mitochondrial outer membranes utilizing porphyrins as endogenous ligands.
    FASEB J. 1987 Oct;1(4):282-8 PMID: 2820823
  10. Purification and characterization of a protein associated with peripheral-type benzodiazepine binding sites.
    J Biol Chem. 1988 Nov 25;263(33):17317-21 PMID: 2846560
  11. Peripheral-type benzodiazepine receptors in endocrine organs: autoradiographic localization in rat pituitary, adrenal, and testis.
    Endocrinology. 1985 Feb;116(2):567-73 PMID: 2981667
  12. The peripheral-type benzodiazepine receptor. Localization to the mitochondrial outer membrane.
    J Biol Chem. 1986 Jan 15;261(2):576-83 PMID: 3001071
  13. Solubilization and reassembly of the mitochondrial benzodiazepine receptor.
    Biochemistry. 1986 Apr 22;25(8):2120-5 PMID: 3011077
  14. Conserved structural domains among species and tissues-specific differences in the mitochondrial phosphate-transport protein and the ADP/ATP carrier.
    Biochim Biophys Acta. 1986 Dec 3;852(2-3):306-14 PMID: 3022808
  15. Porphyrins are endogenous ligands for the mitochondrial (peripheral-type) benzodiazepine receptor.
    Proc Natl Acad Sci U S A. 1987 Apr;84(8):2256-60 PMID: 3031675
  16. Molecular aspects of the adenine nucleotide carrier from mitochondria.
    Arch Biochem Biophys. 1989 Apr;270(1):1-14 PMID: 2648994
  17. Nucleotide sequence, organization, and nature of the protein products of the carotenoid biosynthesis gene cluster of Rhodobacter capsulatus.
    Mol Gen Genet. 1989 Apr;216(2-3):254-68 PMID: 2747617
  18. Modification of the peripheral-type benzodiazepine receptor by arachidonate, diethylpyrocarbonate and thiol reagents.
    Eur J Pharmacol. 1987 Nov 17;143(3):305-14 PMID: 2826190
  19. Characterization of porphyrin interactions with peripheral type benzodiazepine receptors.
    Mol Pharmacol. 1988 Dec;34(6):800-5 PMID: 2849047
  20. Diethylstilbestrol. A novel F0-directed probe of the mitochondrial proton ATPase.
    J Biol Chem. 1986 Feb 5;261(4):1745-52 PMID: 2868005
  21. Peripheral-type benzodiazepine receptors: autoradiographic localization in whole-body sections of neonatal rats.
    J Pharmacol Exp Ther. 1985 May;233(2):517-26 PMID: 2987488
  22. Hexokinase receptor complex in hepatoma mitochondria: evidence from N,N'-dicyclohexylcarbodiimide-labeling studies for the involvement of the pore-forming protein VDAC.
    Biochemistry. 1986 Mar 11;25(5):1015-21 PMID: 3008816
  23. AHN 086: an irreversible ligand of "peripheral" benzodiazepine receptors.
    Mol Pharmacol. 1986 Jun;29(6):540-5 PMID: 3012318
  24. Enrichment and biochemical characterization of boundary membrane contact sites from rat-liver mitochondria.
    Biochim Biophys Acta. 1986 Sep 11;860(3):672-89 PMID: 3017427
  25. Photoaffinity labeling of peripheral-type benzodiazepine-binding sites.
    Mol Pharmacol. 1987 Jan;31(1):42-9 PMID: 3027525
  26. The GABAA/benzodiazepine receptor is a heterotetramer of homologous alpha and beta subunits.
    EMBO J. 1987 Mar;6(3):561-5 PMID: 3034594
  27. Partial purification and pharmacology of peripheral-type benzodiazepine receptors.
    J Recept Res. 1987;7(1-4):55-70 PMID: 3040984
  28. Influence of Ca2+ on the isolation from rat brain mitochondria of a fraction enriched of boundary membrane contact sites.
    Cell Calcium. 1988 Aug;9(4):159-65 PMID: 3191526
  29. Measurement of protein using bicinchoninic acid.
    Anal Biochem. 1985 Oct;150(1):76-85 PMID: 3843705
  30. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
    Nature. 1970 Aug 15;227(5259):680-5 PMID: 5432063
  31. Receptors for the age of anxiety: pharmacology of the benzodiazepines.
    Science. 1980 Jan 18;207(4428):274-81 PMID: 6101294
  32. Proton ATPase of rat liver mitochondria. Preparation and visualization of a functional complex using the novel zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate.
    J Biol Chem. 1984 Apr 10;259(7):4642-51 PMID: 6231296
  33. Purification of a protein having pore forming activity from the rat liver mitochondrial outer membrane.
    Biochem J. 1982 Oct 15;208(1):77-82 PMID: 6297464
  34. Peripheral-type benzodiazepine receptors in the central nervous system: localization to olfactory nerves.
    J Neurosci. 1984 Feb;4(2):593-603 PMID: 6321699
  35. Intracellular localization and properties of particulate hexokinase in the Novikoff ascites tumor. Evidence for an outer mitochondrial membrane location.
    J Biol Chem. 1983 Sep 25;258(18):10904-12 PMID: 6885806
  36. Functional significance of mitochondrial bound hexokinase in tumor cell metabolism. Evidence for preferential phosphorylation of glucose by intramitochondrially generated ATP.
    J Biol Chem. 1988 Nov 25;263(33):17422-8 PMID: 3182854
  37. Solubilization and hydrodynamic properties of pig atrial muscarinic acetylcholine receptor in dodecyl beta-D-maltoside.
    Biochem J. 1988 Oct 15;255(2):553-60 PMID: 3202834
  38. A film detection method for tritium-labelled proteins and nucleic acids in polyacrylamide gels.
    Eur J Biochem. 1974 Jul 1;46(1):83-8 PMID: 4850204
  39. Silver staining of proteins in polyacrylamide gels.
    Anal Biochem. 1981 Nov 15;118(1):197-203 PMID: 6175245
  40. In situ molecular weight determination of brain and peripheral benzodiazepine binding sites.
    Eur J Pharmacol. 1981 Dec 17;76(4):465-6 PMID: 6276201
  41. The use of a zwitterionic detergent in two-dimensional gel electrophoresis of trout liver microsomes.
    Anal Biochem. 1983 Dec;135(2):453-5 PMID: 6660519
  42. Uncoupling of oxidative phosphorylation by cadmium ion.
    J Biol Chem. 1956 Nov;223(1):147-56 PMID: 13376584
  43. Specific benzodiazepine receptors in rat brain characterized by high-affinity (3H)diazepam binding.
    Proc Natl Acad Sci U S A. 1977 Sep;74(9):3805-9 PMID: 20632
  44. Phosphate transport in rat liver mitochondria. Energy-dependent accumulation of phosphate by inverted inner membrane vesicles.
    J Biol Chem. 1978 Dec 10;253(23):8598-603 PMID: 152316
  45. The mitochondrial benzodiazepine receptor: evidence for association with the voltage-dependent anion channel (VDAC).
    J Bioenerg Biomembr. 1992 Feb;24(1):63-9 PMID: 1380506
  46. Peripheral-type benzodiazepine receptors: a second site of action for benzodiazepines.
    Neuropsychopharmacology. 1991 Jun;4(4):237-44 PMID: 1678259
  47. Electrophysiological characterization of contact sites in brain mitochondria.
    J Biol Chem. 1990 Jan 15;265(2):908-13 PMID: 1688556
  48. Release of Ca2+ from heart and kidney mitochondria by peripheral-type benzodiazepine receptor ligands.
    Int J Biochem. 1991;23(2):207-13 PMID: 1847885
  49. Alkyl glucosides as effective solubilizing agents for bovine rhodopsin. A comparison with several commonly used detergents.
    Biochim Biophys Acta. 1976 Feb 19;426(1):46-56 PMID: 1247624
  50. Mammalian peripheral-type benzodiazepine receptor is homologous to CrtK protein of rhodobacter capsulatus, a photosynthetic bacterium.
    Cell. 1991 May 31;65(5):721-2 PMID: 1645618
  51. The peripheral-type benzodiazepine receptor is functionally linked to Leydig cell steroidogenesis.
    J Biol Chem. 1990 Mar 5;265(7):3772-9 PMID: 2154488
  52. Peripheral-type benzodiazepine receptors mediate translocation of cholesterol from outer to inner mitochondrial membranes in adrenocortical cells.
    J Biol Chem. 1990 Sep 5;265(25):15015-22 PMID: 2168398
  53. Glucose phosphorylation in tumor cells. Cloning, sequencing, and overexpression in active form of a full-length cDNA encoding a mitochondrial bindable form of hexokinase.
    J Biol Chem. 1990 Apr 15;265(11):6481-8 PMID: 2318862
  54. Mitochondrial benzodiazepine receptors mediate inhibition of mitochondrial respiratory control.
    Mol Pharmacol. 1989 Jan;35(1):157-63 PMID: 2464128
  55. Characterization of a peripheral-type benzodiazepine-binding site in the mitochondria of Chinese hamster ovary cells.
    FEBS Lett. 1989 Mar 13;245(1-2):238-44 PMID: 2538361
  56. Effects of peripheral benzodiazepines upon the O2 consumption of neuroblastoma cells.
    Eur J Pharmacol. 1989 Feb 28;161(2-3):197-202 PMID: 2542045
  57. Interaction of non-classical detergents with the mitochondrial porin. A new purification procedure and characterization of the pore-forming unit.
    Eur J Biochem. 1989 Jul 15;183(1):179-87 PMID: 2546771
  58. Inhibition of substrate oxidation in mitochondria by the peripheral-type benzodiazepine receptor ligand AHN 086.
    Biochem Pharmacol. 1991 May 15;41(10):1479-84 PMID: 1850277
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.89.8.3170
Published
1992-04-15
Pages
3170-4
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC48827
Subset
IM
Grants
NIDA NIH HHS · DA-00074 · United States
NIDA NIH HHS · DA-00266 · United States
External Links
PubMed source DOI: 10.1073/pnas.89.8.3170 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2