Considering the data presented in this review, we propose that the steroidogenic pool of cholesterol enters the channel formed by the 18 kD PBR protein and transfers from the outer leaflet of the outer mitochondrial membrane to the inner leaflet of the outer membrane. This activity may be directly stimulated by hormones via modulation of the PBR affinity for the endogenous ligand DBI, which is continuously present around the mitochondria (100). Hormone or cAMP-induced changes in PBR affinity will lead to changes in PBR topography and the rapid formation of contact sites between the outer and inner mitochondrial membranes. Thus, cholesterol will be transported "passively" from the outer to the inner membrane. On the mitochondrial membrane contact-site formation, we should also consider here the role of DBI as an acyl-CoA binding protein (90). DBI was shown to mediate intermembrane transport of long-chain acyl-CoA esters (104) and fatty acylation has been proposed as a mechanism employed in transport processes that require fusion of lipid bilayers (105). Thus, DBI may induce the formation of additional contact sites.

It is evident that the presence of tissue-specific PBR-associated proteins may provide selectivity and sensitivity to the PBR function. In addition, it should be noted that the model proposed here does not exclude the presence of additional mechanisms, such as guanosine triphosphate (GTP) and calcium, involved in the process of the acute regulation of steroidogenesis (46,106,107). Identifying and understanding the role of each component of the mitochondrial cholesterol transport apparatus and then their interaction and relationship should allow us to put together the puzzle of the acute regulation of steroidogenesis by hormones. This puzzle is even more complex in the brain because we have no information on the extracellular signal(s) regulating brain neurosteroid synthesis.

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