PT  - JOURNAL ARTICLE
AU  - Shuliang Chen
AU  - Melissa A. Roberts
AU  - Chun-Yuan Chen
AU  - Sebastian Markmiller
AU  - Hong-Guang Wei
AU  - Gene W. Yeo
AU  - James G Granneman
AU  - James A. Olzmann
AU  - Susan Ferro-Novick
TI  - VPS13A and VPS13C influence lipid droplet abundance
AID  - 10.1101/2022.06.21.497109
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.06.21.497109
4099  - http://biorxiv.org/content/early/2022/06/23/2022.06.21.497109.short
4100  - http://biorxiv.org/content/early/2022/06/23/2022.06.21.497109.full
AB  - Lipid transfer proteins mediate the exchange of lipids between closely apposed membranes at organelle contact sites and play key roles in lipid metabolism, membrane homeostasis, and cellular signaling. A recently discovered novel family of lipid transfer proteins, which includes the VPS13 proteins (VPS13A-D), adopt a rod-like bridge conformation with an extended hydrophobic groove that enables the bulk transfer of membrane lipids for membrane growth. Loss of function mutations in VPS13A and VPS13C cause chorea acanthocytosis and Parkinson’s disease, respectively. VPS13A and VPS13C localize to multiple organelle contact sites, including endoplasmic reticulum (ER) – lipid droplet (LD) contact sites, but the functional roles of these proteins in LD regulation remains mostly unexplored. Here, we employ CRISPR-Cas9 genome editing to generate VPS13A and VPS13C knockout cell lines in U-2 OS cells via deletion of exon 2 and introduction of an early frameshift. Analysis of LD content in these cell lines revealed that loss of either VPS13A or VPS13C results in reduced LD abundance under oleate-stimulated conditions. These data implicate VPS13A and VPS13C in LD regulation and raise the intriguing possibility that VPS13A and VPS13C-mediated lipid transfer facilitates LD biogenesis.Competing Interest StatementJ.A.O. is a member of the scientific advisory board for Vicinitas Therapeutics. G.W.Y. is a co-founder, member of the board of directors, equity holder, and paid consultant for Locanabio and Eclipse Bioinnovations. G.W.Y. is a Distinguished Visiting Professor at the National University of Singapore. The terms of these arrangements have been reviewed and approved by the University of California, San Diego in accordance with its conflict-of-interest policies. The authors declare no other competing interests.