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

Abstract

The F1F0-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 F1F0 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 F0 and F1 domains. A cross-bridging protein density was resolved which connects the two F0 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 IF1 inhibitor protein.F1F0 dimer ͉ electron microscopy ͉ protein bridge

Combined defects in oxidative phosphorylation and fatty acid β-oxidation in mitochondrial disease

“…Further research resulted in the isolation of a supercomplex containing CIII/CIV 2 in several strains of bacteria [10][11][12] and CI/CIII 2 , CIII 2 , CI 2 /CIV and CI/CIII 2 /CIV with varying stoichiometry in potato mitochondria [13,14]. In yeast, a CV dimer (CV 2 ) [15] and CIII 2 /CIV 1-2 supercomplex have also been detected [16].…”

H2‐Fueled ATP Synthesis on an Electrode: Mimicking Cellular Respiration

“…The average number of protrusions per cm 2 estimated from the AFM images is 2×10 10 . However, their size is not homogeneous and is larger than expected for individual molecules, indicating that each protrusion is likely to include more than one protein 21. The MW of the F 1 F 0 ‐ATPase is ≈500 kD, so the expected mass increase for the average number of protrusions observed is indeed ≈18 ng cm −2 .…”

Assessing Actual Contribution of IF1, Inhibitor of Mitochondrial FoF1, to ATP Homeostasis, Cell Growth, Mitochondrial Morphology, and Cell Viability

“…When cells are deprived of oxygen and glucose, IF1-suppressed cells lose cellular ATP and die more rapidly than control cells, suggesting a role of IF1 in maintaining ATP concentration ([ATP]) in energy crises (9). Several groups reported that IF1 facilitates dimer formation of F o F 1 in the inner mitochondrial membranes (10 -12) and contributes to cristae formation (9,(13)(14)(15)(16)(17)(18). This profound effect of IF1 on mitochondrial morphology remains controversial (19,20).…”