Bioenergy: new features of ATP synthesis

The mitochondrial ATP synthase is a large molecular energy conversion machine that utilizes electrochemical potential across the bioenergy membrane called cristae. This potential is conserved by the membrane curvature induced by ATP synthase grouped in bipods. The diodes that make up the bioenergy membrane are thought to be universal across eukaryotes. Two recent studies of cryo-EM by Kock-Flygaard et al and Mühleip et al of Alexey Amunts’ laboratory identified different types of ATP synthase upregulation.

The ATP synthase structure of ciliates revealed binaries, which, unlike all of the complexes previously examined, the two parts embedded in the membrane are not identical with each other. The commonly observed symmetry is broken by aligning a single subunit in the dimer interface securing the damper. In addition, ATP synthase has an unusual U-shaped arrangement, thus membrane curvature formation is achieved through the tetramerization process. Therefore, this work defines the tetra-synthase ATP as the intact skeletal unit that spreads cristae formation in ciliates.

The investigation of the infectious apicomplexan parasites showed Toxoplasma, that ATP synthase is arranged in a cyclic hexagonal form. However, within the hexagon, the lipid bilayer was found to be close to the plane, which is not sufficient to form the bioenergetic membrane. Therefore, the cryo-tomography method was applied to the original membranes isolated from the mitochondria of the parasites, which revealed that the hexagons are also arranged in a higher order of organization. In particular, 20 ATP synthase units are linked together in large arrays of decimal symmetry. They form pentagonal pyramids with the size of 20 Mega Dalton. At the center of each pyramid, hexagonal ATP synthase levels are directed at 40 degrees. Therefore, the mechanism of the pentagonal pyramids generates the morphology of the cristae in a manner that differs from the canonical binaries which are believed to be universal.

Finally, structural studies identified a major subunit ATPTG11 that holds hexagons together. Subunit removal showed loss of pentagonal pyramids, skew shaped crests, and defective growth of parasites. This demonstrates that the unique molecular arrangement is essential for maintaining vital energy in the Apicomplexa.

Together, these studies demonstrate the structural basis for the diversity of the membrane-forming properties of ATP formulations in mitochondria. It is this that the basic mechanism of ATP synthase differs between eukaryotic strains.



Flygaard RK, Mühleip A, Tobiasson V, Amunts A. Type III ATP synthase is a symmetrically skewed binary that leads to membrane curvature through tetramerization. Nature Communications. 2020; Eleven.

Muhleip A, Kock Flygaard R, Ovciarikova J, Lacombe A, Fernandes P, Sheiner L, and Amunts A. Hexagonal ATP synthase groups form the form of mitochondria of Toxoplasma. Nature Communications. 2021; 12.

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