1. Evolutionary Biology
  2. Structural Biology and Molecular Biophysics

Structure of a mitochondrial ATP synthase with bound native cardiolipin

  1. Alexander Mühleip
  2. Sarah E McComas
  3. Alexey Amunts  Is a corresponding author
  1. Stockholm University, Sweden
https://doi.org/10.7554/eLife.51179
Share this article
Cite this article
  1. Alexander Mühleip
  2. Sarah E McComas
  3. Alexey Amunts
(2019)
Structure of a mitochondrial ATP synthase with bound native cardiolipin
eLife 8:e51179.
https://doi.org/10.7554/eLife.51179
  2. Download BibTeX
  3. Download .RIS

Abstract

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 interaction 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.

Data availability

All data generated or analyzed during this study are included in this Article and the Supplementary Information. The cryo-EM maps have been deposited in the Electron Microscopy Data Bank with accession codes EMD-10467, EMD-10468, EMD-10469, EMD-10470, EMD 10471, EMD-10472, EMD-10473, EMD-10474, EMD-10475. The atomic models have been deposited in the Protein Data Bank under accession codes 6TDU, 6TDV, 6TDW, 6TDX, 6TDY, 6TDZ, 6TE0.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Alexander Mühleip

    Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Solna, Sweden
    Competing interests
    The authors declare that no competing interests exist.

  2. Sarah E McComas

    Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Solna, Sweden
    Competing interests
    The authors declare that no competing interests exist.

  3. Alexey Amunts

    Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Solna, Sweden
    For correspondence
    amunts@scilifelab.se
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5302-1740

Funding

Stiftelsen för Strategisk Forskning (FFL15:0325)

  • Alexey Amunts

Ragnar Söderbergs stiftelse (M44/16)

  • Alexey Amunts

Vetenskapsrådet (NT_2015-04107)

  • Alexey Amunts

Cancerfonden (2017/1041)

  • Alexey Amunts

H2020 European Research Council (ERC-2018-StG-805230)

  • Alexey Amunts

Knut och Alice Wallenbergs Stiftelse ((2018.0080)

  • Alexey Amunts

European Molecular Biology Organization (ALTF 260-2017)

  • Alexander Mühleip

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2019, Mühleip et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 13,550
    views
  • 1,163
    downloads
  • 76
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Alexander Mühleip
  2. Sarah E McComas
  3. Alexey Amunts
(2019)
Structure of a mitochondrial ATP synthase with bound native cardiolipin
eLife 8:e51179.
https://doi.org/10.7554/eLife.51179

Share this article

https://doi.org/10.7554/eLife.51179

Categories and tags

Further reading

    1. Evolutionary Biology
    2. Genetics and Genomics

    Single-cell eQTL mapping in yeast reveals a tradeoff between growth and reproduction

    James Boocock, Noah Alexander ... Leonid Kruglyak
    Research Article

    Expression quantitative trait loci (eQTLs) provide a key bridge between noncoding DNA sequence variants and organismal traits. The effects of eQTLs can differ among tissues, cell types, and cellular states, but these differences are obscured by gene expression measurements in bulk populations. We developed a one-pot approach to map eQTLs in Saccharomyces cerevisiae by single-cell RNA sequencing (scRNA-seq) and applied it to over 100,000 single cells from three crosses. We used scRNA-seq data to genotype each cell, measure gene expression, and classify the cells by cell-cycle stage. We mapped thousands of local and distant eQTLs and identified interactions between eQTL effects and cell-cycle stages. We took advantage of single-cell expression information to identify hundreds of genes with allele-specific effects on expression noise. We used cell-cycle stage classification to map 20 loci that influence cell-cycle progression. One of these loci influenced the expression of genes involved in the mating response. We showed that the effects of this locus arise from a common variant (W82R) in the gene GPA1, which encodes a signaling protein that negatively regulates the mating pathway. The 82R allele increases mating efficiency at the cost of slower cell-cycle progression and is associated with a higher rate of outcrossing in nature. Our results provide a more granular picture of the effects of genetic variants on gene expression and downstream traits.

    1. Ecology
    2. Evolutionary Biology

    First evidence for the evolution of host manipulation by tumors during the long-term vertical transmission of tumor cells in Hydra oligactis

    Justine Boutry, Océane Rieu ... Fréderic Thomas
    Research Article

    While host phenotypic manipulation by parasites is a widespread phenomenon, whether tumors, which can be likened to parasite entities, can also manipulate their hosts is not known. Theory predicts that this should nevertheless be the case, especially when tumors (neoplasms) are transmissible. We explored this hypothesis in a cnidarian Hydra model system, in which spontaneous tumors can occur in the lab, and lineages in which such neoplastic cells are vertically transmitted (through host budding) have been maintained for over 15 years. Remarkably, the hydras with long-term transmissible tumors show an unexpected increase in the number of their tentacles, allowing for the possibility that these neoplastic cells can manipulate the host. By experimentally transplanting healthy as well as neoplastic tissues derived from both recent and long-term transmissible tumors, we found that only the long-term transmissible tumors were able to trigger the growth of additional tentacles. Also, supernumerary tentacles, by permitting higher foraging efficiency for the host, were associated with an increased budding rate, thereby favoring the vertical transmission of tumors. To our knowledge, this is the first evidence that, like true parasites, transmissible tumors can evolve strategies to manipulate the phenotype of their host.

    1. Evolutionary Biology
    2. Microbiology and Infectious Disease

    Secondary structure of the SARS-CoV-2 genome is predictive of nucleotide substitution frequency

    Zach Hensel
    Short Report

    Accurate estimation of the effects of mutations on SARS-CoV-2 viral fitness can inform public-health responses such as vaccine development and predicting the impact of a new variant; it can also illuminate biological mechanisms including those underlying the emergence of variants of concern. Recently, Lan et al. reported a model of SARS-CoV-2 secondary structure and its underlying dimethyl sulfate reactivity data (Lan et al., 2022). I investigated whether base reactivities and secondary structure models derived from them can explain some variability in the frequency of observing different nucleotide substitutions across millions of patient sequences in the SARS-CoV-2 phylogenetic tree. Nucleotide basepairing was compared to the estimated ‘mutational fitness’ of substitutions, a measurement of the difference between a substitution’s observed and expected frequency that is correlated with other estimates of viral fitness (Bloom and Neher, 2023). This comparison revealed that secondary structure is often predictive of substitution frequency, with significant decreases in substitution frequencies at basepaired positions. Focusing on the mutational fitness of C→U, the most common type of substitution, I describe C→U substitutions at basepaired positions that characterize major SARS-CoV-2 variants; such mutations may have a greater impact on fitness than appreciated when considering substitution frequency alone.