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@ARTICLE{Vercellino:1038811,
author = {Vercellino, Irene and Sazanov, Leonid A.},
title = {{SCAF}1 drives the compositional diversity of mammalian
respirasomes},
journal = {Biochimica et biophysica acta / Bioenergetics},
volume = {1865},
issn = {0005-2728},
address = {Amsterdam},
publisher = {Elsevier},
reportid = {FZJ-2025-01648},
pages = {149113 -},
year = {2024},
abstract = {The ATP synthase in themitochondria of each human being
generatesabout 50 kg of ATP daily, maintaining a steady
state level of about 10 g tosustain life. The enzyme has a
rotarymechanism to transmit energy froma transmembrane
proton motive force across the inner membrane of
theorganelle (derived by respiration) to the catalytic sites
where ATP isformed from ADP and phosphate. The bovine enzyme
is made of 29protein subunits of 18 types, including the
inhibitor protein IF1 [1,2]. Theyare organised into a rotor
and a stator. The rotor consists of a membranebound c8-ring
attached to a central stalk (subunits γ, δ and ε)
thatprotrudes into the mitochondrialmatrix, and penetrates
into the sphericalcatalytic domain (α3β3) of the stator.
The stator is completed by aperipheral stalk (PS; subunits
OSCP, F6, b and d), bound to the externalsurface of the
catalytic domain and extending into themembrane
domain(subunits ATP6 and ATP8 plus three small membrane
subunits e, f and g,which form a wedge encapsulating lipid
molecules). ATP6 is intimatelyassociated with the c8-ring
and provides two proton half channelsinvolved in the
generation of rotation. The wedges in two ATP
synthasesinteract to formthe characteristic dimers that sit
on the tips of the cristaeand subunit k links dimers
together. The assembly of the human enzymeinvolves the
formation of intermediate modules representing (i)
thecatalytic domain (α3β3γδε, or F1, plus IF1), (ii)
the PS plus the membrane"wedge". [3,4], and (iii)
themembrane bound c8-rotor ring [5]. They formthe key
intermediate F1-IF1-c8-PS [5] into which subunits ATP6 and
ATP8are inserted between the c8-ring and the wedge with
subunit j bound toATP6, forming the proton pathway. Two
protein assembly factors arerequired to build the c8-ring
and three others to assemble the catalyticdomain. IF1 is
another key assembly factor that intervenes to
preventpartially formed complexes that are capable of ATP
hydrolysis (but notsynthesis) from doing so. The assembly
pathway reflects the probablemodular path of evolution of
the enzyme. Finally, I will comment on thelack of
involvement of ATP synthase in the permeability transition.},
cin = {ER-C-3},
ddc = {570},
cid = {I:(DE-Juel1)ER-C-3-20170113},
pnm = {5352 - Understanding the Functionality of Soft Matter and
Biomolecular Systems (POF4-535) / 5241 - Molecular
Information Processing in Cellular Systems (POF4-524)},
pid = {G:(DE-HGF)POF4-5352 / G:(DE-HGF)POF4-5241},
typ = {PUB:(DE-HGF)16},
UT = {WOS:001311206700011},
doi = {10.1016/j.bbabio.2024.149113},
url = {https://juser.fz-juelich.de/record/1038811},
}