Structure of a complete ATP synthase dimer reveals the molecular basis of inner mitochondrial membrane morphology

Journal article

We determined the structure of a complete, dimeric F1Fo-ATP synthase from yeast Yarrowia lipolytica mitochondria by a combination of cryo-EM and X-ray crystallography. The final structure resolves 58 of the 60 dimer subunits. Horizontal helices of subunit a in Fo wrap around the c-ring rotor, and a total of six vertical helices assigned to subunits a, b, f, i, and 8 span the membrane. Subunit 8 (A6L in human) is an evolutionary derivative of the bacterial b subunit. On the lumenal membrane surface, subunit f establishes direct contact between the two monomers. Comparison with a cryo-EM map of the F1Fo monomer identifies subunits e and g at the lateral dimer interface. They do not form dimer contacts but enable dimer formation by inducing a strong membrane curvature of ∼100°. Our structure explains the structural basis of cristae formation in mitochondria, a landmark signature of eukaryotic cell morphology. ATP synthases are complex macromolecular machines that supply most of the ATP in cells. Hahn et al. present the structure of a complete ATP synthase dimer, which provides insights into both the mechanism of these nanomotors and how they cause membrane bending to form cristae in the inner mitochondrial membrane.

Authors: Hahn, A; Parey, K; Bublitz, M; Mills, D; Zickermann, V

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Molecular Cell
• Volume: 63
• Issue: 3
• Pages: 445-456
• Publication date: 2016-08-04
• Acceptance date: 2016-05-26
• DOI: 10.1016/j.molcel.2016.05.037
• EISSN: 1097-4164
• ISSN: 1097-2765
• Keywords: F1Fo-ATP synthase dimer; cryoelectron microscopy; bioenergetics; membrane protein complex; rotary ATPase mechanism; yeast Yarrowia lipolyticar; mitochondria; inner membrane morphology; X-ray crystallography