Figure 4.

Postulated role of STAT3 in mitochondria. STAT3 may function directly or indirectly (e.g., by serving as a scaffolding protein for the posttranslational modification of a subunit protein) as a rheostat to ensure complex I function and prevent excessive ROS production, which would feedback and cause damage to complex I. STAT3 may also interact with cyclophilin D and thereby prevent opening of the mitochondrial permeability transition pore (mPTP) and subsequent disruption of mitochondrial integrity and function through the influx of solutes and water. Additional sites within the ETC where STAT3 may have positive functional actions, include complex II and ATP synthase (complex V). A possible engagement of STAT3 with complex V is postulated based on the observation that complex V activity is markedly reduced with STAT3 loss in Ras-transformed cells (120) and recent evidence identifying mPTP as the c-subunit of the F₁F_O ATP synthase (147).