bims-resufa 2024-01-07 papers

Issue of 2024‒01‒07
two papers selected by
Gavin McStay, Liverpool John Moores University

Biochem J. 2024 Jan 02. pii: BCJ20230450. [Epub ahead of print]

The consequence of ATP synthase dimer angle on mitochondrial morphology studied by cryo-electron tomography.

Emma Buzzard, Mathew McLaren, Piotr Bragoszewski, Andrea Brancaccio, Holly Ford, Bertram Daum, Patricia Kuwabara, Ian Collinson, Vicki Gold.

Mitochondrial ATP synthases form rows of dimers, which induce membrane curvature to give cristae their characteristic lamellar or tubular morphology. The angle formed between the central stalks of ATP synthase dimers varies between species. Using cryo-electron tomography and sub-tomogram averaging, we determined the structure of the ATP synthase dimer from the nematode worm C. elegans and show that the dimer angle differs from previously determined structures. The consequences of this species-specific difference at the dimer interface were investigated by comparing C. elegans and S. cerevisiae mitochondrial morphology. We reveal that C. elegans has a larger ATP synthase dimer angle with more lamellar (flatter) cristae when compared to yeast. The underlying cause of this difference was investigated by generating an atomic model of the C. elegans ATP synthase dimer by homology modelling. A comparison of our C. elegans model to an existing S. cerevisiae structure reveals the presence of extensions and rearrangements in C. elegans subunits associated with maintaining the dimer interface. We speculate that increasing dimer angles could provide an advantage for species that inhabit variable-oxygen environments by forming flatter more energetically efficient cristae.

Keywords: alphafold; atp synthase; cryo-electron microscopy; mitochondria; sub-tomogram averaging

DOI: https://doi.org/10.1042/BCJ20230450

J Biol Chem. 2023 Dec 28. pii: S0021-9258(23)02632-7. [Epub ahead of print] 105603

Large-scale column-free purification of bovine F-ATP synthase.

Chimari Jiko, Yukio Morimoto, Tomitake Tsukihara, Christoph Gerle.

Mammalian F-ATP synthase is central to mitochondrial bioenergetics and is present in the inner mitochondrial membrane in a dynamic oligomeric state of higher oligomers, tetramers, dimers and monomers. In vitro investigations of mammalian F-ATP synthase are often limited by the ability to purify the oligomeric forms present in vivo at a quantity, stability and purity that meets the demand of the planned experiment. We developed a purification approach for the isolation of bovine F-ATP synthase from heart muscle mitochondria that uses a combination of buffer conditions favoring IF1 binding and sucrose density gradient ultracentrifugation to yield stable complexes at high purity in the milligram range. By tuning the glyco-diosgenin (GDN) to lauryl maltose neopentyl glycol (LMNG) ratio in a final gradient, fractions that are either enriched in tetrameric or monomeric F-ATP synthase can be obtained. It is expected that this large-scale column-free purification strategy broadens the spectrum of in vitro investigation on mammalian F-ATP synthase.

Keywords: F-ATP synthase oligomer; bioenergetics; gradient centrifugation; membrane protein; mitochondria; purification; rotary ATPase; supercomplex

DOI: https://doi.org/10.1016/j.jbc.2023.105603