Year: 2013
Type: article
Abstract: Lipid droplets (LDs) are the major fat storage organelles in eukaryotic cells, but how their size is regulated is unknown. Using genetic screens in C. elegans for LD morphology defects in intestinal cells, we found that mutations in atlastin, a GTPase required for homotypic fusion of endoplasmic reticulum (ER) membranes, cause not only ER morphology defects, but also a reduction in LD size. Similar results were obtained after depletion of atlastin or expression of a dominant-negative mutant, whereas overexpression of atlastin had the opposite effect. Atlastin depletion in Drosophila fat bodies also reduced LD size and decreased triglycerides in whole animals, sensitizing them to starvation. In mammalian cells, co-overexpression of atlastin-1 and REEP1, a paralog of the ER tubule-shaping protein DP1/REEP5, generates large LDs. The effect of atlastin-1 on LD size correlates with its activity to promote membrane fusion in vitro. Our results indicate that atlastin-mediated fusion of ER membranes is important for LD size regulation.
Source: Cell Reports
Authors: Robin W. Klemm, Justin P. Norton, Ronald A. Cole, Chen S. Li, Seong H. Park, Matthew M. Crane, Liying Li, Diana Jin, Alexandra Boye-Doe, Tina Y. Liu, Yoko Shibata, Hang Lu, Tom A. Rapoport, Robert V. Farese, Craig Blackstone, Yi Guo, Ho Yi Mak
Institutions: Harvard University, Stowers Institute for Medical Research, National Institutes of Health, National Institute of Neurological Disorders and Stroke, Georgia Institute of Technology, University of Minnesota, University of California, San Francisco, Mayo Clinic, University of Kansas Medical Center
Language: English
Subfield: Biochemistry
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Awards: Identification of Genes that Regulate Cellular Lipid Storage, Quantitative microscopy-based rapid phenotyping and screening, Role of DGAT in Triacyglycerol Metabolism, The Mechanisms of Lipid Droplet Formation and Regulation, Sources, transmission and effects of transcriptional noise in C. elegans aging, Diabetes Research Center, UCSF Liver Center
OpenAlex ID: W1984651084