Dimers of mitochondrial ATP synthase induce membrane curvature and self-assemble into rows
Thorsten B. Blum, Alexander Hahn, Thomas Meier, Karen M. Davies, and Werner Kühlbrandt
PNAS published ahead of print February 13, 2019
Edited by David J. DeRosier, Brandeis University, Waltham, MA, and approved January 3, 2019 (received for review September 25, 2018)
Proteoliposomes of reconstituted Y. lipolytica ATP synthase dimers. (A and C) ATP synthase dimers (yellow) form rows that bend the lipid bilayer (light blue). Insets shows cross-sections (white lines), indicating that dimer rows bend the lipid bilayer by ∼90° (dashed red lines). (B) Flat membrane regions are devoid of ATP synthase. (D) Parallel rows of bidirectionally inserted dimers bend the bilayer into a corrugated sheet. (Scale bars, 100 nm.)
Significance
The ATP synthase in the inner membrane of mitochondria generates most of the ATP that enables higher organisms to live. The inner membrane forms deep invaginations called cristae. Mitochondrial ATP synthases are dimeric complexes of two identical monomers. It is known that the ATP synthase dimers form rows along the tightly curved cristae ridges. Computer simulations suggest that the dimer rows bend the membrane locally, but this has not been shown experimentally. In this study, we use electron cryotomography to provide experimental proof that ATP synthase dimers assemble spontaneously into rows upon membrane reconstitution, and that these rows bend the membrane. The assembly of ATP synthase dimers into rows is most likely the first step in the formation of mitochondrial cristae.
Abstract
Mitochondrial ATP synthases form dimers, which assemble into long ribbons at the rims of the inner membrane cristae. We reconstituted detergent-purified mitochondrial ATP synthase dimers from the green algae Polytomella sp. and the yeast Yarrowia lipolytica into liposomes and examined them by electron cryotomography. Tomographic volumes revealed that ATP synthase dimers from both species self-assemble into rows and bend the lipid bilayer locally. The dimer rows and the induced degree of membrane curvature closely resemble those in the inner membrane cristae. Monomers of mitochondrial ATP synthase reconstituted into liposomes do not bend membrane visibly and do not form rows. No specific lipids or proteins other than ATP synthase dimers are required for row formation and membrane remodelling. Long rows of ATP synthase dimers are a conserved feature of mitochondrial inner membranes. They are required for cristae formation and a main factor in mitochondrial morphogenesis.
mitochondria ATP synthase membrane curvature electron cryotomography subtomogram averaging
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