2. Academic Validation
  3. Human VPS13A is associated with multiple organelles and influences mitochondrial morphology and lipid droplet motility

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

  • Elife. 2019 Feb 11;8:e43561. doi: 10.7554/eLife.43561.
Wondwossen M Yeshaw 1,  Marianne van der Zwaag 1,  Francesco Pinto 1,  Liza L Lahaye 1,  Anita Ie Faber 1,  Rubén Gómez-Sánchez 1,  Amalia M Dolga 2,  Conor Poland 3,  Anthony P Monaco 3 4,  Sven Cd van IJzendoorn 1,  Nicola A Grzeschik 1,  Antonio Velayos-Baeza 3,  Ody Cm Sibon 1
Affiliations

Affiliations

  • 1 Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • 2 Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy (GRIP), Faculty of Science and Engineering, University of Groningen, Groningen, The Netherlands.
  • 3 Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.
  • 4 Office of the President, Tufts University, Medford, United States.
PMID: 30741634 DOI: 10.7554/eLife.43561
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.

Keywords

D. melanogaster; VPS13A; cell biology; endoplasmic reticulum; human; lipid droplets; membrane contact sites; mitochondria.

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