1. Biochemistry and Chemical Biology
  2. Cell Biology
Download icon

An evidence based hypothesis on the existence of two pathways of mitochondrial crista formation

  1. Max E Harner  Is a corresponding author
  2. Ann-Katrin Unger
  3. Willie JC Geerts
  4. Muriel Mari
  5. Toshiaki Izawa
  6. Maria Stenger
  7. Stefan Geimer
  8. Fulvio Reggiori
  9. Benedikt Westermann
  10. Walter Neupert  Is a corresponding author
  1. Max Planck Institute of Biochemistry, Germany
  2. Universität Bayreuth, Germany
  3. Universiteit Utrecht, Netherlands
  4. University of Groningen, Netherlands
Research Article
  • Cited 42
  • Views 3,284
  • Annotations
Cite this article as: eLife 2016;5:e18853 doi: 10.7554/eLife.18853

Abstract

Metabolic function and architecture of mitochondria are intimately linked. More than 60 years ago, cristae were discovered as characteristic elements of mitochondria that harbor the protein complexes of oxidative phosphorylation, but how cristae are formed, remained an open question. Here we present experimental results obtained with yeast that support a novel hypothesis on the existence of two molecular pathways that lead to generation of lamellar and tubular cristae. Formation of lamellar cristae depends on the mitochondrial fusion machinery through a pathway that is required also for homeostasis of mitochondria and mitochondrial DNA. Tubular cristae are formed via invaginations of the inner boundary membrane by a pathway independent of the fusion machinery. Dimerization of the F1FO-ATP synthase and presence of the MICOS complex are necessary for both pathways. The proposed hypothesis is suggested to apply also to higher eukaryotes, since the key components are conserved in structure and function throughout evolution.

Article and author information

Author details

  1. Max E Harner

    Max Planck Institute of Biochemistry, Martinsried, Germany
    For correspondence
    max.harner@med.uni-muenchen.de
    Competing interests
    The authors declare that no competing interests exist.
  2. Ann-Katrin Unger

    Cell Biology and Electron Microscopy, Universität Bayreuth, Bayreuth, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Willie JC Geerts

    Biomolecular Imaging, Bijvoet Center, Universiteit Utrecht, Utrecht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  4. Muriel Mari

    Department of Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  5. Toshiaki Izawa

    Max Planck Institute of Biochemistry, Martinsried, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Maria Stenger

    Cell Biology and Electron Microscopy, Universität Bayreuth, Bayreuth, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Stefan Geimer

    Cell Biology and Electron Microscopy, Universität Bayreuth, Bayreuth, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Fulvio Reggiori

    Department of Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  9. Benedikt Westermann

    Cell Biology and Electron Microscopy, Universität Bayreuth, Bayreuth, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2991-1604
  10. Walter Neupert

    Max Planck Institute of Biochemistry, Martinsried, Germany
    For correspondence
    Neupert@biochem.mpg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0571-4419

Funding

Max-Planck-Gesellschaft

  • Max E Harner
  • Ann-Katrin Unger
  • Toshiaki Izawa
  • Walter Neupert

Carl Friedrich von Siemens Stiftung

  • Walter Neupert

Jung-Stiftung für Wissenschaft und Forschung

  • Max E Harner

Ludwig-Maximilians-Universität München

  • Max E Harner

Netherlands organization for Scientific Research (DN82-303)

  • Fulvio Reggiori

Deutsche Forschungsgemeinschaft (DN82-303)

  • Fulvio Reggiori

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (CRSII3_154421)

  • Fulvio Reggiori

ZonMw (ZonMW VICI)

  • Fulvio Reggiori

Netherlands organization for Scientific Research (822.02.014)

  • Fulvio Reggiori

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

Reviewing Editor

  1. Nikolaus Pfanner, University of Freiburg, Germany

Publication history

  1. Received: June 15, 2016
  2. Accepted: November 14, 2016
  3. Accepted Manuscript published: November 16, 2016 (version 1)
  4. Version of Record published: December 5, 2016 (version 2)

Copyright

© 2016, Harner 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

  • 3,284
    Page views
  • 844
    Downloads
  • 42
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.

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)

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

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

Further reading

    1. Biochemistry and Chemical Biology
    2. Cell Biology
    Mikel Garcia-Marcos
    Research Article Updated

    It has become evident that activation of heterotrimeric G-proteins by cytoplasmic proteins that are not G-protein-coupled receptors (GPCRs) plays a role in physiology and disease. Despite sharing the same biochemical guanine nucleotide exchange factor (GEF) activity as GPCRs in vitro, the mechanisms by which these cytoplasmic proteins trigger G-protein-dependent signaling in cells have not been elucidated. Heterotrimeric G-proteins can give rise to two active signaling species, Gα-GTP and dissociated Gβγ, with different downstream effectors, but how non-receptor GEFs affect the levels of these two species in cells is not known. Here, a systematic comparison of GPCRs and three unrelated non-receptor proteins with GEF activity in vitro (GIV/Girdin, AGS1/Dexras1, and Ric-8A) revealed high divergence in their contribution to generating Gα-GTP and free Gβγ in cells directly measured with live-cell biosensors. These findings demonstrate fundamental differences in how receptor and non-receptor G-protein activators promote signaling in cells despite sharing similar biochemical activities in vitro.

    1. Biochemistry and Chemical Biology
    2. Microbiology and Infectious Disease
    Zachary F Mandell et al.
    Research Article

    NusA and NusG are transcription factors that stimulate RNA polymerase pausing in Bacillus subtilis. While NusA was known to function as an intrinsic termination factor in B. subtilis, the role of NusG in this process was unknown. To examine the individual and combinatorial roles that NusA and NusG play in intrinsic termination, Term-seq was conducted in wild type, NusA depletion, DnusG, and NusA depletion DnusG strains. We determined that NusG functions as an intrinsic termination factor that works alone and cooperatively with NusA to facilitate termination at 88% of the 1400 identified intrinsic terminators. Our results indicate that NusG stimulates a sequence-specific pause that assists in the completion of suboptimal terminator hairpins with weak terminal A-U and G-U base pairs at the bottom of the stem. Loss of NusA and NusG leads to global misregulation of gene expression and loss of NusG results in flagella and swimming motility defects.