(54) THE ROLE OF THE MITOCHONDRIAL BENZODIAZEPINE RECEPTOR IN APOPTOTIC SIGNALING

Maureen W. McEnery (1), Gary Fiskum (2) and Stefan J. Dubel (1)
(1) Case Western Reserve University, Cleveland, OH 44106
(2) University of Maryland School of Medicine, Baltimore, MD 21201

The mitochondrial benzodiazepine receptor (mBzR) is comprised of a novel 18 kDa protein termed the PK11195 binding protein (PKBP), the voltage-dependent anion channel (VDAC) and the adenine nucleotide transporter (McEnery et al., 1992; McEnery, 1992; McEnery et al., 1993). The subunit composition suggested a topography similar to mitochondrial contact sites - protein complexes which connect the outer and inner mitochondrial membrane and suggested to function as control sites of metabolite transport. Studies have suggested that the level of expression of PKBP is dynamically regulated following differentiation of 3T3 cells, in models of lymphocyte activation and following ischemia. Recent interest in the contribution of outer mitochondrial membrane proteins in apoptotic signaling (bcl-2/bax) has raised the question as to whether bcl-2/bax are functioning alone or in concert with resident proteins of the outer mitochondrial membrane. To address this question, we have begun to examine possible interactions between PKBP and bcl-2 family members. The potential involvement of mBzR in apoptotic signaling offers a unique perspective from which to investigate the role of outer mitochondrial membrane proteins in programmed cell death.