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

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 reticul...

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Autores principales: Yeshaw, Wondwossen M, van der Zwaag, Marianne, Pinto, Francesco, Lahaye, Liza L, Faber, Anita IE, Gómez-Sánchez, Rubén, Dolga, Amalia M, Poland, Conor, Monaco, Anthony P, van IJzendoorn, Sven CD, Grzeschik, Nicola A, Velayos-Baeza, Antonio, Sibon, Ody CM
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389287/
https://www.ncbi.nlm.nih.gov/pubmed/30741634
http://dx.doi.org/10.7554/eLife.43561
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author Yeshaw, Wondwossen M
van der Zwaag, Marianne
Pinto, Francesco
Lahaye, Liza L
Faber, Anita IE
Gómez-Sánchez, Rubén
Dolga, Amalia M
Poland, Conor
Monaco, Anthony P
van IJzendoorn, Sven CD
Grzeschik, Nicola A
Velayos-Baeza, Antonio
Sibon, Ody CM
author_facet Yeshaw, Wondwossen M
van der Zwaag, Marianne
Pinto, Francesco
Lahaye, Liza L
Faber, Anita IE
Gómez-Sánchez, Rubén
Dolga, Amalia M
Poland, Conor
Monaco, Anthony P
van IJzendoorn, Sven CD
Grzeschik, Nicola A
Velayos-Baeza, Antonio
Sibon, Ody CM
author_sort Yeshaw, Wondwossen M
collection PubMed
description 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.
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spelling pubmed-63892872019-02-27 Human VPS13A is associated with multiple organelles and influences mitochondrial morphology and lipid droplet motility Yeshaw, Wondwossen M van der Zwaag, Marianne Pinto, Francesco Lahaye, Liza L Faber, Anita IE Gómez-Sánchez, Rubén Dolga, Amalia M Poland, Conor Monaco, Anthony P van IJzendoorn, Sven CD Grzeschik, Nicola A Velayos-Baeza, Antonio Sibon, Ody CM eLife Cell Biology 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. eLife Sciences Publications, Ltd 2019-02-11 /pmc/articles/PMC6389287/ /pubmed/30741634 http://dx.doi.org/10.7554/eLife.43561 Text en © 2019, Yeshaw et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Yeshaw, Wondwossen M
van der Zwaag, Marianne
Pinto, Francesco
Lahaye, Liza L
Faber, Anita IE
Gómez-Sánchez, Rubén
Dolga, Amalia M
Poland, Conor
Monaco, Anthony P
van IJzendoorn, Sven CD
Grzeschik, Nicola A
Velayos-Baeza, Antonio
Sibon, Ody CM
Human VPS13A is associated with multiple organelles and influences mitochondrial morphology and lipid droplet motility
title Human VPS13A is associated with multiple organelles and influences mitochondrial morphology and lipid droplet motility
title_full Human VPS13A is associated with multiple organelles and influences mitochondrial morphology and lipid droplet motility
title_fullStr Human VPS13A is associated with multiple organelles and influences mitochondrial morphology and lipid droplet motility
title_full_unstemmed Human VPS13A is associated with multiple organelles and influences mitochondrial morphology and lipid droplet motility
title_short Human VPS13A is associated with multiple organelles and influences mitochondrial morphology and lipid droplet motility
title_sort human vps13a is associated with multiple organelles and influences mitochondrial morphology and lipid droplet motility
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389287/
https://www.ncbi.nlm.nih.gov/pubmed/30741634
http://dx.doi.org/10.7554/eLife.43561
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