Speaker: Dr. Ruth Slack Associate Professor, Dept. of Medicine, Neuroscience Group, University of Ottawa, Canada The AIF-Opa1 link, connecting mitochondrial structure to apoptosis signaling The mitochondrial protein Apoptosis-inducing factor (AIF) is a redox active flavoprotein that has dual roles in the regulation of cell death and survival. We have previously identified a novel role for AIF in controling mitochondrial structure. We have examined the mechanism by which AIF controls mitochondrial structure and metabolism. AIF deficiency results in mitochondrial fragmentation, cristae malformation and a defect in oxidative phosporylation. Mitochondrial AIF is essential for organelle fusion as the fission/fusion proteins Mfn1 and dnDrp1 fail to rescue the structural defect seen in AIF deficiency. In contrast, upregulation of Opa1 in AIF deficient neurons restores mitochondrial structure, metabolism and cellular survival. We show that AIF functions upstream of Opa1 because increased mitochondrial AIF cannot rescue neuronal cell death induced by Opa1 deficiency. AIF deficient neurons display reduced Opa1 oligomerization resulting in impaired cristae formation. Furthermore, we show that AIF physically interacts with Opa1 to maintain Opa1 oligomerization. This interaction is critical during apoptosis signaling, as Opa1 oligomerization can be preserved by maintaining mitochondrial AIF. These results identify a novel functional interaction between AIF and Opa1 that links the control of mitochondrial structure with apoptosis signaling during the progression of cell death.