Assembly of the peripheral stalk of ATP synthase in human mitochondria.
Proceedings of the National Academy of Sciences of the United States of America
National Academy of Sciences
MetadataShow full item record
He, J., Carroll, J., Ding, S., Fearnley, I. M., Montgomery, M., & Walker, J. (2020). Assembly of the peripheral stalk of ATP synthase in human mitochondria.. Proceedings of the National Academy of Sciences of the United States of America, 117 (47), 29602-29608. https://doi.org/10.1073/pnas.2017987117
The ATP synthase in human mitochondria is a membrane bound assembly of 29 proteins of 18 kinds organized into F1-catalytic, peripheral stalk (PS) and c8-rotor ring modules. All but two membrane components are encoded in nuclear genes, synthesized on cytoplasmic ribosomes, imported into the mitochondrial matrix, and assembled into the complex with the mitochondrial gene products, ATP6 and ATP8. Intermediate vestigial ATPase complexes formed by disruption of nuclear genes for individual subunits provide a description of how the various domains are introduced into the enzyme. From this approach, it is evident that three alternative pathways operate to introduce the PS module (including associated membrane subunits e, f and g). In one pathway, the PS is built up by addition to the core subunit b of membrane subunits e and g together, followed by membrane subunit f. Then this b-e-g-f complex is bound to the preformed F1-c8 module by subunits OSCP and F6. The final component of the PS, subunit d, is added subsequently to form a key intermediate that accepts the two mitochondrially encoded subunits. In another route to this key intermediate, first e and g together and then f are added to a pre-formed F1-c8-OSCP-F6-b-d complex. A third route involves the addition of the c8-ring module to the complete F1-PS complex. The key intermediate then accepts the two mitochondrially encoded subunits, stabilized by the addition of subunit j, leading to an ATP synthase complex that is coupled to the proton motive force and capable of making ATP.
Cell Line, Mitochondria, Humans, Proton-Translocating ATPases, Mitochondrial Proton-Translocating ATPases, Mitochondrial Proteins, Protein Subunits, Adenosine Triphosphate, HEK293 Cells
Embargo Lift Date
External DOI: https://doi.org/10.1073/pnas.2017987117
This record's URL: https://www.repository.cam.ac.uk/handle/1810/311697
All rights reserved