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

• Published in: eLife Vol. 8
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 11.02.2019; eLife Sciences Publications, Ltd
• Subjects: Cell Biology; Chorea; Endoplasmic reticulum; Endoplasmic Reticulum - genetics; Endoplasmic Reticulum - metabolism; Endosomes - genetics; Exports; Genetic engineering; Homeostasis; Humans; lipid droplets; Lipid Droplets - metabolism; Lipids; Localization; Mammalian cells; membrane contact sites; Membrane proteins; Mitochondria; Mitochondria - genetics; Mitochondria - metabolism; Mitochondrial Membranes - metabolism; Mutation; Neuroacanthocytosis - genetics; Neurodegenerative diseases; Neurodegenerative Diseases - genetics; Organelles; Protein Domains; Proteins; Vesicular Transport Proteins - genetics; Vesicular Transport Proteins - metabolism; VPS13A; United States > US; Netherlands; cell biology; membrane contact sites; mitochondria; VPS13A; D. melanogaster; lipid droplets; human; endoplasmic reticulum
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.43561

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.