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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eLife Sciences Publications Ltd
2019-02-01
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| Online Access: | https://elifesciences.org/articles/43561 |
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doaj-82c95e0d7eb64c9cabeaa87ffdcdcbf42021-05-05T17:24:13ZengeLife Sciences Publications LtdeLife2050-084X2019-02-01810.7554/eLife.43561Human VPS13A is associated with multiple organelles and influences mitochondrial morphology and lipid droplet motilityWondwossen M Yeshaw0https://orcid.org/0000-0002-3134-3458Marianne van der Zwaag1Francesco Pinto2Liza L Lahaye3Anita IE Faber4Rubén Gómez-Sánchez5https://orcid.org/0000-0002-8274-3259Amalia M Dolga6Conor Poland7Anthony P Monaco8Sven CD van IJzendoorn9Nicola A Grzeschik10Antonio Velayos-Baeza11https://orcid.org/0000-0002-7717-4477Ody CM Sibon12https://orcid.org/0000-0002-6836-6063Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, The NetherlandsDepartment of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, The NetherlandsDepartment of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, The NetherlandsDepartment of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, The NetherlandsDepartment of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, The NetherlandsDepartment of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, The NetherlandsDepartment of Molecular Pharmacology, Groningen Research Institute of Pharmacy (GRIP), Faculty of Science and Engineering, University of Groningen, Groningen, The NetherlandsWellcome Trust Centre for Human Genetics, Oxford, United KingdomWellcome Trust Centre for Human Genetics, Oxford, United Kingdom; Office of the President, Tufts University, Medford, United StatesDepartment of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, The NetherlandsDepartment of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, The NetherlandsWellcome Trust Centre for Human Genetics, Oxford, United KingdomDepartment of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, The NetherlandsThe 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.https://elifesciences.org/articles/43561VPS13Aendoplasmic reticulummitochondrialipid dropletsmembrane contact sites |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Wondwossen M Yeshaw Marianne van der Zwaag Francesco Pinto Liza L Lahaye Anita IE Faber Rubén Gómez-Sánchez Amalia M Dolga Conor Poland Anthony P Monaco Sven CD van IJzendoorn Nicola A Grzeschik Antonio Velayos-Baeza Ody CM Sibon |
| spellingShingle |
Wondwossen M Yeshaw Marianne van der Zwaag Francesco Pinto Liza L Lahaye Anita IE Faber Rubén Gómez-Sánchez Amalia M Dolga Conor Poland Anthony P Monaco Sven CD van IJzendoorn Nicola A Grzeschik Antonio Velayos-Baeza Ody CM Sibon Human VPS13A is associated with multiple organelles and influences mitochondrial morphology and lipid droplet motility eLife VPS13A endoplasmic reticulum mitochondria lipid droplets membrane contact sites |
| author_facet |
Wondwossen M Yeshaw Marianne van der Zwaag Francesco Pinto Liza L Lahaye Anita IE Faber Rubén Gómez-Sánchez Amalia M Dolga Conor Poland Anthony P Monaco Sven CD van IJzendoorn Nicola A Grzeschik Antonio Velayos-Baeza Ody CM Sibon |
| author_sort |
Wondwossen M Yeshaw |
| title |
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_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_sort |
human vps13a is associated with multiple organelles and influences mitochondrial morphology and lipid droplet motility |
| publisher |
eLife Sciences Publications Ltd |
| series |
eLife |
| issn |
2050-084X |
| publishDate |
2019-02-01 |
| 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. |
| topic |
VPS13A endoplasmic reticulum mitochondria lipid droplets membrane contact sites |
| url |
https://elifesciences.org/articles/43561 |
| work_keys_str_mv |
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