AIF, reactive oxygen species, and neurodegeneration: A “complex” problem

► Recombinant AIF does not function as an antioxidant enzyme. ► AIF deficiency causes a reduction in mitochondrial complex I. ► Changes in ROS are more likely due to electron transport changes than loss of AIF. ► AIF deficient mice do not get Parkinson's disease despite reduced complex I. ► AIF has pro-survival and pro-death roles that both modulate neuronal injury.