Human VPS13A is associated with multiple organelles and influences mitochondrial morphology and lipid droplet motility

  1. Wondwossen M Yeshaw
  2. Marianne van der Zwaag
  3. Francesco Pinto
  4. Liza L Lahaye
  5. Anita IE Faber
  6. Rubén Gómez-Sánchez
  7. Amalia M Dolga
  8. Conor Poland
  9. Antony P Monaco
  10. Sven van IJzendoorn
  11. Nicola A Grzeschik
  12. Antonio Velayos-Baeza
  13. Ody CM Sibon  Is a corresponding author
  1. University Medical Center Groningen, Netherlands
  2. Wellcome Trust Centre for Human Genetics, United Kingdom
  3. Tufts University, United States

Abstract

The VPS13A gene is associated with the neurodegenerative disorder Chorea Acanthocytosis. It is unknown what the consequences are of impaired function of VPS13A at the subcellular level. We demonstrate that VPS13A is a peripheral membrane protein, associated with mitochondria, the endoplasmic reticulum and lipid droplets. VPS13A is localized at sites where the endoplasmic reticulum and mitochondria are in close contact. VPS13A interacts with the ER residing protein VAP-A via its FFAT domain. Interaction with mitochondria is mediated via its C-terminal domain. In VPS13A-depleted cells, ER-mitochondria contact sites are decreased, mitochondria are fragmented and mitophagy is decreased. VPS13A also localizes to lipid droplets and affects lipid droplet motility. In VPS13A-depleted mammalian cells lipid droplet numbers are increased. Our data, together with recently published data from others, indicate that VPS13A is required for establishing membrane contact sites between various organelles to enable lipid transfer required for mitochondria and lipid droplet related processes.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Wondwossen M Yeshaw

    Department of Cell Biology, University Medical Center Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  2. Marianne van der Zwaag

    Department of Cell Biology, University Medical Center Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  3. Francesco Pinto

    Department of Cell Biology, University Medical Center Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  4. Liza L Lahaye

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

    Department of Cell Biology, University Medical Center Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  6. Rubén Gómez-Sánchez

    Department of Cell Biology, University Medical Center Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8274-3259
  7. Amalia M Dolga

    Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  8. Conor Poland

    Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Antony P Monaco

    Tufts University, Medford, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Sven van IJzendoorn

    Department of Cell Biology, University Medical Center Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  11. Nicola A Grzeschik

    Department of Cell Biology, University Medical Center Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  12. Antonio Velayos-Baeza

    Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7717-4477
  13. Ody CM Sibon

    Department of Cell Biology, University Medical Center Groningen, Groningen, Netherlands
    For correspondence
    o.c.m.sibon@umcg.nl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6836-6063

Funding

Wellcome (090532/Z/09/Z)

  • Antonio Velayos-Baeza

Nederlandse Organisatie voor Wetenschappelijk Onderzoek (865.10.012)

  • Ody CM Sibon

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

Reviewing Editor

  1. Agnieszka Chacinska, University of Warsaw, Poland

Version history

  1. Received: November 12, 2018
  2. Accepted: February 10, 2019
  3. Accepted Manuscript published: February 11, 2019 (version 1)
  4. Version of Record published: February 25, 2019 (version 2)

Copyright

© 2019, Yeshaw 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.

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  1. Wondwossen M Yeshaw
  2. Marianne van der Zwaag
  3. Francesco Pinto
  4. Liza L Lahaye
  5. Anita IE Faber
  6. Rubén Gómez-Sánchez
  7. Amalia M Dolga
  8. Conor Poland
  9. Antony P Monaco
  10. Sven van IJzendoorn
  11. Nicola A Grzeschik
  12. Antonio Velayos-Baeza
  13. Ody CM Sibon
(2019)
Human VPS13A is associated with multiple organelles and influences mitochondrial morphology and lipid droplet motility
eLife 8:e43561.
https://doi.org/10.7554/eLife.43561

Share this article

https://doi.org/10.7554/eLife.43561

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