Research study supports the view that ATP synthase arose via independent evolution of its three constituent structural modules

Human ATP synthase is a molecular rotary machine built from twenty-eight subunits of seventeen kinds, two encoded in mitochondrial DNA, fifteen in the nucleus. A team led by John Walker has provided further evidence that assembly proceeds via construction of its three constituent modules, the F₁-module, the peripheral stalk and the c₈-rotor ring. In a recent paper published in the EMBO Journal they show that:

• The catalytic F₁-module can be assembled independently of other subunits of the enzyme.
• The F₁-module is built by introduction of the three α-subunits and the three β-subunits in alternation around either a pre-assembled central stalk or a preassembled rotor complex.
• The assembly factor assisted entry of α- and β-subunits proceeds via different mechanisms.
• The assembly process avoids making intermediate complexes that could either hydrolyze ATP or uncouple mitochondria by dissipating the proton motive force.
• The modular assembly process supports the view that the ATP synthase arose via independent evolution of its modules.

Publication Reference:

He, J., Carroll, J., Ding, S. et al. Assembly of the catalytic module and the rotor of human ATP synthase. EMBO J (2026).

https://doi.org/10.1038/s44318-026-00842-9

Figure legend. A and B: Co-existing alternative pathways for assembly of the rotor and incorporation of the central stalk into human ATP synthase.