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Seipin is required for converting nascent to mature lipid droplets
- Source :
- eLife, eLife, eLife Sciences Publication, 2016, 5, ⟨10.7554/eLife.16582⟩, eLife, Vol 5 (2016), Wang, H, Becuwe, M, Housden, B E, Chitraju, C, Porras, A J, Graham, M M, Liu, X N, Thiam, A R, Savage, D B, Agarwal, A K, Garg, A, Olarte, M-J, Lin, Q, Fröhlich, F, Hannibal-Bach, H K, Upadhyayula, S, Perrimon, N, Kirchhausen, T, Ejsing, C S, Walther, T C & Farese, R V 2016, ' Seipin is required for converting nascent to mature lipid droplets ', eLife, vol. 5, e16582 . https://doi.org/10.7554/eLife.16582
- Publication Year :
- 2016
- Publisher :
- HAL CCSD, 2016.
-
Abstract
- How proteins control the biogenesis of cellular lipid droplets (LDs) is poorly understood. Using Drosophila and human cells, we show here that seipin, an ER protein implicated in LD biology, mediates a discrete step in LD formation—the conversion of small, nascent LDs to larger, mature LDs. Seipin forms discrete and dynamic foci in the ER that interact with nascent LDs to enable their growth. In the absence of seipin, numerous small, nascent LDs accumulate near the ER and most often fail to grow. Those that do grow prematurely acquire lipid synthesis enzymes and undergo expansion, eventually leading to the giant LDs characteristic of seipin deficiency. Our studies identify a discrete step of LD formation, namely the conversion of nascent LDs to mature LDs, and define a molecular role for seipin in this process, most likely by acting at ER-LD contact sites to enable lipid transfer to nascent LDs. DOI: http://dx.doi.org/10.7554/eLife.16582.001<br />eLife digest Living organisms often store energy in the form of fat molecules called triglycerides. Enzymes in a compartment of the cell called the endoplasmic reticulum catalyze the chemical reactions needed to make these triglycerides. The cell then stores the triglycerides in a different structure called the lipid droplet. Lipid droplets form from the endoplasmic reticulum in an organized manner, but little is known about the cellular machinery that gives rise to lipid droplets. A protein called seipin is thought to be involved in lipid droplet formation. Seipin resides in the endoplasmic reticulum and a shortage of this protein in cells leads to abnormal lipid droplets – that is, cells often have lots of tiny lipid droplets or a few giant ones. People who lack seipin lose much of their fat tissue and instead store fat in the wrong places, such as the liver. Now, Wang et al. have studied the seipin protein in insect and human cells grown in the laboratory. The experiments confirmed that cells that lack the seipin protein form lots of tiny dot-like structures containing triglycerides that fail to grow into normal-sized lipid droplets. These lipid droplets have different proteins on their surface, which may impair their ability to store fat. Wang et al. also discovered that in normal cells, the seipin protein is found at distinct spots in the endoplasmic reticulum. This distribution appears to allow seipin to come into contact with the small, newly formed lipid droplets and enable them to grow. Together these findings suggest that the seipin protein could form part of a molecular machine that allows more triglycerides to be added into newly formed lipid droplets causing the droplets to grow as normal. When seipin is not present the newly formed lipid droplets initially become stuck in a smaller form. As a consequence, a few of these tiny droplets later enter a different cellular pathway of lipid droplet expansion, which turns them into abnormally large lipid droplets. Future challenges will be to determine precisely how seipin enables newly formed lipid droplets to grow. It will also be important to confirm whether seipin works with other proteins as part of a molecular machine and, if so, to investigate how these proteins affect the formation and growth of lipid droplets. DOI: http://dx.doi.org/10.7554/eLife.16582.002
- Subjects :
- 0301 basic medicine
endocrine system
QH301-705.5
Science
[SDV]Life Sciences [q-bio]
lipid droplet
Economic shortage
Biology
complex mixtures
General Biochemistry, Genetics and Molecular Biology
Seipin
03 medical and health sciences
Lipid droplet
cell biology
lipid metabolism
human
Biology (General)
LiveDrop
General Immunology and Microbiology
D. melanogaster
General Neuroscience
Endoplasmic reticulum
technology, industry, and agriculture
A protein
Lipid metabolism
General Medicine
eye diseases
Cell biology
endoplasmic reticulum
030104 developmental biology
seipin
Large lipid droplets
Medicine
Organelle biogenesis
organelle biogenesis
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 2050084X
- Database :
- OpenAIRE
- Journal :
- eLife, eLife, eLife Sciences Publication, 2016, 5, ⟨10.7554/eLife.16582⟩, eLife, Vol 5 (2016), Wang, H, Becuwe, M, Housden, B E, Chitraju, C, Porras, A J, Graham, M M, Liu, X N, Thiam, A R, Savage, D B, Agarwal, A K, Garg, A, Olarte, M-J, Lin, Q, Fröhlich, F, Hannibal-Bach, H K, Upadhyayula, S, Perrimon, N, Kirchhausen, T, Ejsing, C S, Walther, T C & Farese, R V 2016, ' Seipin is required for converting nascent to mature lipid droplets ', eLife, vol. 5, e16582 . https://doi.org/10.7554/eLife.16582
- Accession number :
- edsair.doi.dedup.....e8f2cf79891debf671824e35253cd59e