Human VPS13A is associated with multiple organelles and influences mitochondrial morphology and lipid droplet motility
- University Medical Center Groningen, Netherlands
- Wellcome Trust Centre for Human Genetics, United Kingdom
- 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
Rubén Gómez-Sánchez
Antonio Velayos-Baeza
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
- Agnieszka Chacinska, University of Warsaw, Poland
Version history
- Received: November 12, 2018
- Accepted: February 10, 2019
- Accepted Manuscript published: February 11, 2019 (version 1)
- 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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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
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