ATP synthase structure, rotary mechanism and dimers
ATP synthase is the enzyme that makes most ATP in living cells. Kubo and Takada describe it as two rotary motors, one driven by protons in the membrane and one catalytic, sharing a central rotor. Protons cross the membrane only by turning the c-ring.8 In mitochondria the enzyme also forms dimers, which Kühlbrandt links to the cristae and Kaludercic and Giorgio link to the permeability transition pore.36
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Structure of the dimer
Kühlbrandt (2015) reviewed a mitochondrial ATP synthase dimer solved by single-particle cryo-EM at 6–7 Å resolution.1 The map showed a hairpin of long, membrane-intrinsic helices in the a-subunit beside the Fo rotor ring. It also showed aqueous half-channels on either side of the membrane for proton movement.2 The cryo-EM map was combined with fitted high-resolution X-ray structures of the catalytic F1 head and the rotor ring in the membrane. The review says this gives the first complete picture of this complex.2 Preiss and colleagues, citing a structural study of the a-subunit from the alga Polytomella, report that its membrane-embedded helices lie horizontal relative to the c-ring.4
The rotary mechanism
Kubo and Takada (2022) set out the layout of the Fo motor. The c-subunit oligomer is a ring that serves as the rotor. The a-subunit is the stator and passes protons between the ring and the aqueous space outside the membrane.8 They state that the a-subunit has two half-channels, one open to each side. Because the two are not directly connected, protons can cross the membrane only when the c-ring rotates. Proton passage is therefore coupled to rotation of the ring.8
Alkaliphiles and rival coupling
Preiss and colleagues discuss bacteria that grow at high pH. Sequences of their a-subunits differ from those of bacteria that prefer neutral pH. K180 in helix 4 was hypothesised to slow proton loss from the entry half-channel.5 In the earliest mutagenesis study, replacing K180 with glycine cost growth on malate at pH 10.5 but not at 7.5.5 Morelli and colleagues argue for a different picture. They propose proton currents along the membrane surface that reach the a-subunit and give localized coupling. They say this excludes an osmotic nature for the process.7
Dimers, cristae and the pore
Kühlbrandt's review shows ATP synthase dimer rows along shallow inner membrane ridges in ageing mitochondria, where the cristae recede into the boundary membrane.3 Rao and colleagues (2026) place the dimers at the cristae tips, close to the proton pumps on the slopes.9 Kaludercic and Giorgio (2016) note the finding that ATP synthase dimers form the permeability transition pore. They say this makes it easier to identify the sites behind the enzyme's two functions.6
The structure of a mitochondrial ATP synthase dimer has now been determined by single-particle cryo-EM at 6–7 Å resolution [39].
Kühlbrandt W, 2015 · Structure and function of mitochondrial membrane protein complexes · open at passage 18Surprisingly, the structure revealed a hairpin of long, membrane-intrinsic α-helices in the a-subunit next to the Fo rotor ring, as well as aqueous half-channels on either side of the membrane for proton translocation.
Kühlbrandt W, 2015 · Structure and function of mitochondrial membrane protein complexes · open at passage 18In ageing mitochondria, the cristae recede into the boundary membrane, with ATP synthases dimer rows along the shallow inner membrane ridges.
Kühlbrandt W, 2015 · Structure and function of mitochondrial membrane protein complexes · open at passage 28Recently, a structural study of the a-subunit from the algae Polytomella sp., which has a dimeric F-type ATP synthase structure, has shown that the membrane-embedded helices of the a-subunit stator are horizontal relative to the c-ring
Preiss L, Hicks DB, Suzuki S, Meier T, Krulwich TA, 2015 · Alkaliphilic Bacteria with Impact on Industrial Applications, Concepts of Early… · open at passage 21In the earliest mutagenesis study, the K180 residue was replaced by glycine, the consensus residue for non-alkaliphiles, resulting in major loss of growth on malate at pH 10.5 but not 7.5
Preiss L, Hicks DB, Suzuki S, Meier T, Krulwich TA, 2015 · Alkaliphilic Bacteria with Impact on Industrial Applications, Concepts of Early… · open at passage 23Recent finding that ATP synthase dimers form the PTP [12] makes the identification of the sites involved in the two different functions of ATP synthase more feasible
Kaludercic N, Giorgio V, 2016 · The Dual Function of Reactive Oxygen/Nitrogen Species in Bioenergetics and Cell… · open at passage 14it appears realistic that complex I may transfer protons from its central part to the periplasmatic side, allowing them to travel on the membrane surface thanks to the heads of phospholipids
Morelli AM, Ravera S, Calzia D, Panfoli I, 2019 · An update of the chemiosmotic theory as suggested by possible proton currents… · open at passage 38Since these two half-channels are not directly connected, protons can only pass through the membrane via rotation of the c-ring.
Kubo S, Takada S, 2022 · Rotational Mechanism of FO Motor in the F-Type ATP Synthase Driven by the… · open at passage 1The highly folded architecture minimizes the diffusion distance between the proton pumps (Complexes I, III, and IV) located on the cristae slopes and the ATP synthase dimers situated at the cristae tips
Rao J, Wan QQ, Chen L, Tang RB, Killedar D, Tay F, Niu LN, 2026 · Cristae: bridging bioenergetic hubs and compartmental barriers in mitochondrial… · open at passage 39