scholarly journals Structure of a mitochondrial ATP synthase with bound native cardiolipin

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Alexander Mühleip ◽  
Sarah E McComas ◽  
Alexey Amunts
Keyword(s):  
Atp Synthase ◽  
Membrane Curvature ◽  
Dimer Interface ◽  
Functional Roles ◽  
Lipid Interactions ◽  
Mitochondrial Atp Synthase ◽  
Distinct Subunit ◽  
Insight Into ◽  
Membrane Region ◽  
Inhibitory Factor 1

The mitochondrial ATP synthase fuels eukaryotic cells with chemical energy. Here we report the cryo-EM structure of a divergent ATP synthase dimer from mitochondria of Euglena gracilis, a member of the phylum Euglenozoa that also includes human parasites. It features 29 different subunits, 8 of which are newly identified. The membrane region was determined to 2.8 Å resolution, enabling the identification of 37 associated lipids, including 25 cardiolipins, which provides insight into protein-lipid interactions and their functional roles. The rotor-stator interface comprises four membrane-embedded horizontal helices, including a distinct subunit a. The dimer interface is formed entirely by phylum-specific components, and a peripherally associated subcomplex contributes to the membrane curvature. The central and peripheral stalks directly interact with each other. Last, the ATPase inhibitory factor 1 (IF1) binds in a mode that is different from human, but conserved in Trypanosomatids.

scholarly journals ATP synthase hexamer assemblies shape cristae of Toxoplasma mitochondria

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Alexander Mühleip ◽  
Rasmus Kock Flygaard ◽  
Jana Ovciarikova ◽  
Alice Lacombe ◽  
Paula Fernandes ◽  
...  
Keyword(s):  
Atp Synthase ◽  
Apical Membrane ◽  
Membrane Curvature ◽  
Structural Basis ◽  
Dimer Interface ◽  
Mitochondrial Atp Synthase ◽  
Subtomogram Averaging

AbstractMitochondrial ATP synthase plays a key role in inducing membrane curvature to establish cristae. In Apicomplexa causing diseases such as malaria and toxoplasmosis, an unusual cristae morphology has been observed, but its structural basis is unknown. Here, we report that the apicomplexan ATP synthase assembles into cyclic hexamers, essential to shape their distinct cristae. Cryo-EM was used to determine the structure of the hexamer, which is held together by interactions between parasite-specific subunits in the lumenal region. Overall, we identified 17 apicomplexan-specific subunits, and a minimal and nuclear-encoded subunit-a. The hexamer consists of three dimers with an extensive dimer interface that includes bound cardiolipins and the inhibitor IF1. Cryo-ET and subtomogram averaging revealed that hexamers arrange into ~20-megadalton pentagonal pyramids in the curved apical membrane regions. Knockout of the linker protein ATPTG11 resulted in the loss of pentagonal pyramids with concomitant aberrantly shaped cristae. Together, this demonstrates that the unique macromolecular arrangement is critical for the maintenance of cristae morphology in Apicomplexa.

Insight into the Bind−Lock Mechanism of the Yeast Mitochondrial ATP Synthase Inhibitory Peptide

Biochemistry ◽  
2007 ◽  
Vol 46 (29) ◽  
pp. 8680-8688 ◽  
Author(s):  
Vincent Corvest ◽  
Claude Sigalat ◽  
Francis Haraux
Keyword(s):  
Atp Synthase ◽  
Inhibitory Peptide ◽  
Mitochondrial Atp Synthase ◽  
Insight Into

scholarly journals An ancestral interaction module promotes oligomerization in divergent mitochondrial ATP synthases

2021 ◽  
Author(s):  
Alexey Amunts ◽  
Ondrej Gahura ◽  
Alexander Muhleip ◽  
Carolina Hierro-Yap ◽  
Brian Panicucci ◽  
...  
Keyword(s):  
Atp Synthase ◽  
Conformational Flexibility ◽  
Membrane Curvature ◽  
Water Molecules ◽  
Rotational States ◽  
Efficient Energy ◽  
Mitochondrial Atp Synthase ◽  
Dimerization Interface ◽  
A Chain ◽  
Ordered Water

Abstract Mitochondrial ATP synthase forms stable dimers arranged into oligomeric assemblies that generate the inner-membrane curvature essential for efficient energy conversion. Here, we report cryo-EM structures of the intact ATP synthase dimer from Trypanosoma brucei in ten different rotational states. The model consists of 25 subunits, including nine lineage-specific, as well as 36 lipids. The rotary mechanism is influenced by the divergent peripheral stalk, conferring a greater conformational flexibility. Proton transfer in the lumenal half-channel occurs via a chain of five ordered water molecules. The dimerization interface is formed by subunit-g that is critical for interactions but not for the catalytic activity. Although overall dimer architecture varies among eukaryotes, we find that subunit-g together with subunit-e form an ancestral oligomerization motif, which is shared between the trypanosomal and mammalian lineages. Therefore, our data defines the subunit-g/e module as a structural component determining ATP synthase oligomeric assemblies.

scholarly journals The Mitochondrial ATP Synthase: Improved Resolution Cryo-EM Model and Insight into the Structure of the Peripheral Stalk Region

2006 ◽  
Vol 12 (S02) ◽  
pp. 368-369
Author(s):  
J Rubinstein
Keyword(s):  
Atp Synthase ◽  
Peripheral Stalk ◽  
Mitochondrial Atp Synthase ◽  
Insight Into

Extended abstract of a paper presented at Microscopy and Microanalysis 2006 in Chicago, Illinois, USA, July 30 – August 3, 2006

scholarly journals An ancestral interaction module promotes oligomerisation in divergent mitochondrial ATP synthases

2021 ◽  
Author(s):  
Ondrej Gahura ◽  
Alexander Muhleip ◽  
Carolina Hierro-Yap ◽  
Brian Panicucci ◽  
Minal Jain ◽  
...  
Keyword(s):  
Atp Synthase ◽  
Conformational Flexibility ◽  
Membrane Curvature ◽  
Water Molecules ◽  
Rotational States ◽  
Efficient Energy ◽  
Mitochondrial Atp Synthase ◽  
Dimerization Interface ◽  
A Chain ◽  
Ordered Water

Mitochondrial ATP synthase forms stable dimers arranged into oligomeric assemblies that generate the inner-membrane curvature essential for efficient energy conversion. Here, we report cryo EM structures of the intact ATP synthase dimer from trypanosomes in 10 different rotational states. The model consists of 25 subunits, including 11 lineage-specific, as well as 36 lipids. The rotary mechanism is influenced by the divergent peripheral stalk, conferring a greater conformational flexibility. Proton transfer in the lumenal half-channel occurs via a chain of five ordered water molecules. The dimerization interface is formed by subunit-g that is critical for interactions but not for the catalytic activity. Although overall dimer architecture varies among eukaryotes, we find that subunit-g and -e form a common ancestral oligomerisation motif, which is shared between the trypanosomal and mammalian lineages. Therefore, our data defines the subunit-g/e module as a structural component determining ATP synthase oligomeric assemblies.

scholarly journals Dimers of mitochondrial ATP synthase induce membrane curvature and self-assemble into rows

2019 ◽  
Vol 116 (10) ◽  
pp. 4250-4255 ◽  
Author(s):  
Thorsten B. Blum ◽  
Alexander Hahn ◽  
Thomas Meier ◽  
Karen M. Davies ◽  
Werner Kühlbrandt
Keyword(s):  
Lipid Bilayer ◽  
Yarrowia Lipolytica ◽  
Atp Synthase ◽  
Membrane Curvature ◽  
Specific Lipids ◽  
Inner Membrane ◽  
Mitochondrial Atp Synthase ◽  
Mitochondrial Morphogenesis ◽  
Electron Cryotomography ◽  
Main Factor

Mitochondrial ATP synthases form dimers, which assemble into long ribbons at the rims of the inner membrane cristae. We reconstituted detergent-purified mitochondrial ATP synthase dimers from the green algaePolytomellasp. and the yeastYarrowia lipolyticainto liposomes and examined them by electron cryotomography. Tomographic volumes revealed that ATP synthase dimers from both species self-assemble into rows and bend the lipid bilayer locally. The dimer rows and the induced degree of membrane curvature closely resemble those in the inner membrane cristae. Monomers of mitochondrial ATP synthase reconstituted into liposomes do not bend membrane visibly and do not form rows. No specific lipids or proteins other than ATP synthase dimers are required for row formation and membrane remodelling. Long rows of ATP synthase dimers are a conserved feature of mitochondrial inner membranes. They are required for cristae formation and a main factor in mitochondrial morphogenesis.

scholarly journals Generation of mitochondrial reactive oxygen species is controlled by ATPase inhibitory factor 1 and regulates cognition

PLoS Biology ◽  
2021 ◽  
Vol 19 (5) ◽  
pp. e3001252
Author(s):  
Pau B. Esparza-Moltó ◽  
Inés Romero-Carramiñana ◽  
Cristina Núñez de Arenas ◽  
Marta P. Pereira ◽  
Noelia Blanco ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Synaptic Transmission ◽  
Atp Synthase ◽  
Reactive Oxygen ◽  
Synaptic Function ◽  
Inhibitory Factor ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species ◽  
Mitochondrial Atp Synthase ◽  
Inhibitory Factor 1

The mitochondrial ATP synthase emerges as key hub of cellular functions controlling the production of ATP, cellular signaling, and fate. It is regulated by the ATPase inhibitory factor 1 (IF1), which is highly abundant in neurons. Herein, we ablated or overexpressed IF1 in mouse neurons to show that IF1 dose defines the fraction of active/inactive enzyme in vivo, thereby controlling mitochondrial function and the production of mitochondrial reactive oxygen species (mtROS). Transcriptomic, proteomic, and metabolomic analyses indicate that IF1 dose regulates mitochondrial metabolism, synaptic function, and cognition. Ablation of IF1 impairs memory, whereas synaptic transmission and learning are enhanced by IF1 overexpression. Mechanistically, quenching the IF1-mediated increase in mtROS production in mice overexpressing IF1 reduces the increased synaptic transmission and obliterates the learning advantage afforded by the higher IF1 content. Overall, IF1 plays a key role in neuronal function by regulating the fraction of ATP synthase responsible for mitohormetic mtROS signaling.

scholarly journals Type III ATP synthase is a symmetry-deviated dimer that induces membrane curvature through tetramerization

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Rasmus Kock Flygaard ◽  
Alexander Mühleip ◽  
Victor Tobiasson ◽  
Alexey Amunts
Keyword(s):  
Atp Synthase ◽  
Single Copy ◽  
Membrane Curvature ◽  
Universal Property ◽  
Membrane Anchor ◽  
Unique Type ◽  
Type Iii ◽  
Mitochondrial Atp Synthase ◽  
Fundamental Phenomenon ◽  
Tetrameric Form

Abstract Mitochondrial ATP synthases form functional homodimers to induce cristae curvature that is a universal property of mitochondria. To expand on the understanding of this fundamental phenomenon, we characterized the unique type III mitochondrial ATP synthase in its dimeric and tetrameric form. The cryo-EM structure of a ciliate ATP synthase dimer reveals an unusual U-shaped assembly of 81 proteins, including a substoichiometrically bound ATPTT2, 40 lipids, and co-factors NAD and CoQ. A single copy of subunit ATPTT2 functions as a membrane anchor for the dimeric inhibitor IF1. Type III specific linker proteins stably tie the ATP synthase monomers in parallel to each other. The intricate dimer architecture is scaffolded by an extended subunit-a that provides a template for both intra- and inter-dimer interactions. The latter results in the formation of tetramer assemblies, the membrane part of which we determined to 3.1 Å resolution. The structure of the type III ATP synthase tetramer and its associated lipids suggests that it is the intact unit propagating the membrane curvature.

Sign in / Sign up

Export Citation Format

Share Document