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

Maureen W. Mcenery, Adele M. Snowman, Rosario R. Trifiletti, Solomon H. Snyder

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)3170-3174
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number8
DOIs
StatePublished - 1992

Keywords

  • Flunitrazepam
  • Isoquinoline carboxamide
  • PK11195
  • PK14105
  • Porphyrins

ASJC Scopus subject areas

  • General

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