Fig. 8.

Working model on the functional significance of a TSPO-NOX2 association in microglia: In this model, we propose that TSPO in the outer mitochondria membrane is able to (1) transfer ferrochelatase synthesized heme from the inner mitochondri membrane to the gp65 precursor of gp91^phox. Once heme has been delivered to gp91^phox, then (2) it is able to dimerize with p22^phox in the ER to: (3) form the gp91^phox = p22^phox and principal catalytic subunit of NOX2, cytochrome b₅₅₈ (Cytb₅₅₈). Once Cytb₅₅₈ forms, then (4) it is able to traffic to the plasma membrane/lipid rafts where it remains dormant until an activating event takes place. (5) NOX2 activation promotes the translocation of the cytosolic subunits p40, p47, p67, and Rac1 to the plasma membrane to form an active NOX2 complex. MAM: mitochondrial associated membrane; Fch: ferrochelatase; IMS: intermembrane space