Work

Assembly of the catalytic module and the rotor of human ATP synthase

Year: 2026

Type: article

Abstract: Human ATP synthase is a molecular rotary machine bound in inner mitochondrial membranes, built from twenty-eight subunits of seventeen kinds, two encoded in mitochondrial DNA, the remainder in nuclear genes. The machine consists of a rotor and an interacting stator. Turning of the rotor driven by a transmembrane proton motive force effects a cycle of structural changes in the catalytic part of the stator, producing three ATP molecules per rotation. Here, to establish how the stator and rotor are assembled, we deleted subunits and known assembly factors from human cells, purified and accumulated assembly intermediate complexes, and characterized them by gel analysis and mass spectrometry, allowing us to propose pathways of assembly of the rotor and the catalytic F 1 -module of the stator. These observations provide opportunities for further development by structural analysis of the accumulated intermediates. The compositions of the various assembly intermediates support the view that ATP synthase arose via independent evolution of its three constituent structural components, the catalytic F 1 -module, the peripheral stalk module, and the membrane-associated F o -module.

Source: The EMBO Journal

DOI: 10.1038/s44318-026-00842-9

Authors: Jiuya He, Joe Carroll, Shujing Ding, Jiao Li, Ian M Fearnley, John E Walker