Reactome | Formation of ATP by chemiosmotic coupling

Formation of ATP by chemiosmotic coupling

Stable Identifier

R-HSA-163210

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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Formation of ATP by chemiosmotic coupling

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The re-entry of protons into the mitochondrial matrix through Complex V causes conformational changes which result in ATP synthesis. Complex V (ATP synthase) is composed of 3 parts; an F1 catalytic core (approx 5 subunits), an F0 membrane proton channel (approx 9 subunits) and two stalks linking F1 to F0. F1 contains three alpha subunits, three beta subunits, and one each of gamma, delta, and epsilon subunits. Each beta subunit contains an active site for ATP synthesis. F0 has at least 9 subunits (a-g, A6L and F6; see Lai et al., 2023; reviewed in Jonckheere et al., 2011).
The mechanism of ATP synthesis by Complex V was predicted by Boyer et al in 1973: ADP and Pi bind to the enzyme resulting in a conformational change. ATP is then synthesized, still bound to the enzyme. Another change in the active site results in the release of free ATP into the matrix. The overall reaction is:
ADP + Pi + H+ + nH+ (intermemb. space) = ATP + H2O + nH+ (matrix)

Mutations in several ATP synthase subunits can lead to different types of mitochondrial complex V deficiency (MC5D; reviewed in Garone et al., 2022; Del Dotto et al., 2024).

Literature References

PubMed ID	Title	Journal	Year
38396915	Variants in Human ATP Synthase Mitochondrial Genes: Biochemical Dysfunctions, Associated Diseases, and Therapies Musiani, F, Solaini, G, Del Dotto, V, Baracca, A	Int J Mol Sci	2024
35330152	From the Structural and (Dys)Function of ATP Synthase to Deficiency in Age-Related Diseases Pietra, A, Nesci, S, Garone, C	Life (Basel)	2022
37244256	Structure of the human ATP synthase Yang, X, Yu, L, Liu, F, Rao, Z, Feng, Z, Gong, H, Gao, Y, Du, Z, Wang, W, Tang, Y, Lai, Y, Xu, J, Zhou, S, Zhang, Y, Guddat, LW, Zhao, Z	Mol Cell	2023
4517936	A new concept for energy coupling in oxidative phosphorylation based on a Boyer, PD, Momsen, W, Cross, RL	Proc Natl Acad Sci U S A	1973
21874297	Mitochondrial ATP synthase: architecture, function and pathology Jonckheere, AI, Rodenburg, RJ, Smeitink, JA	J Inherit Metab Dis	2012