Structure of dimeric mitochondrial ATP synthase: Novel F ₀ bridging features and the structural basis of mitochondrial cristae biogenesis

Abstract

The F 1 F 0 –ATP synthase exists as a dimer in mitochondria, where it is essential for the biogenesis of the inner membrane cristae. How two ATP synthase complexes dimerize to promote cristae formation is unknown. Here we resolved the structure of the dimeric F 1 F 0 ATP synthase complex isolated from bovine heart mitochondria by transmission electron microscopy. The structure of the ATP synthase dimer has an overall conic appearance that is consistent with the proposed role of the dimeric enzyme in mitochondrial cristae biogenesis. The ATP synthase dimer interface is formed by contacts on both the F 0 and F 1 domains. A cross-bridging protein density was resolved which connects the two F 0 domains on the intermembrane space side of the membrane. On the matrix side of the complex, the two F 1 moieties are connected by a protein bridge, which is attributable to the IF 1 inhibitor protein.