Seipin-Mediated Contacts as Gatekeepers of Lipid Flux at the Endoplasmic Reticulum–Lipid Droplet Nexus

Salo, Veijo T.; Hölttä‐Vuori, Maarit; Ikonen, Elina

doi:10.1177/2515256420945820

Cited by 15 publications

(11 citation statements)

References 137 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These observations are in line with our imaging data from fixed cells, showing that a fraction of seipin specifically localizes at mitochondria-ER contact sites. However, we noted that seipin-mitochondria interactions are not as long lasting as seipin-LD interactions, which appear to be stable at least on the minute timescale (Salo et al, 2019(Salo et al, , 2020.…”

Section: Abnormal Mitochondrial Morphology and Reduced Oxygen Consumption In Bscl2 Patients' Cellsmentioning

confidence: 68%

Seipin localizes at endoplasmic-reticulum-mitochondria contact sites to control mitochondrial calcium import and metabolism in adipocytes

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Abnormal Mitochondrial Morphology and Reduced Oxygen Consumption In Bscl2 Patients' Cellsmentioning

confidence: 68%

Seipin localizes at endoplasmic-reticulum-mitochondria contact sites to control mitochondrial calcium import and metabolism in adipocytes

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…Seipin is a critical protein that orchestrates LD formation (Arlt et al, 2021;Chung et al, 2019;Prasanna et al, 2021;Salo et al, 2020;Salo et al, 2019;Wang et al, 2016;Zoni et al, 2021b).…”

Section: Discussionmentioning

confidence: 99%

Seipin transmembrane segments critically function in triglyceride nucleation and lipid droplet budding from the membrane

Kim

Chung

Arlt

et al. 2021

Preprint

View full text Add to dashboard Cite

Lipid droplets (LDs) are organelles formed in the endoplasmic reticulum (ER) to store triacylglycerol (TG) and sterol esters. The ER protein seipin is key for LD biogenesis. Seipin forms a cage-like structure, with each seipin monomer containing a conserved hydrophobic helix (HH) and two transmembrane (TM) segments. How the different parts of seipin function in TG nucleation and LD budding is poorly understood. Here, we utilized molecular dynamics simulations of human seipin, along with cell-based experiments, to study seipin’s functions in protein-lipid interactions, lipid diffusion, and LD maturation. All-atom (AA) simulations indicate that most seipin TM segment residues located in the phospholipid (PL) tail region of the bilayer attract TG. We also find seipin TM segments control lipid diffusion and permeation into the protein complex. Simulating larger, growing LDs with coarse-grained (CG) models, we find that the seipin TM segments form a constricted neck structure to facilitate conversion of a flat oil lens into a budding LD. Using cell experiments and simulations, we also show that conserved, positively charged residues at the end of seipin’s TM segments affect LD maturation. We propose a model in which seipin TM segments critically function in TG nucleation and LD growth.

show abstract

“…Seipin is widely recognized as a key molecular player in LD biogenesis [see ( Salo et al, 2020 ) for a recent comprehensive review]. Seipin is an integral ER membrane protein with two transmembrane domains, exposing both N- and C-termini to the cytosol ( Lundin et al, 2006 ).…”

Section: Disturbances Of Ld Biogenesis In Hsp Pathogenesismentioning

confidence: 99%

Lipid Droplets in the Pathogenesis of Hereditary Spastic Paraplegia

Tadepalle

Rugarli

2021

Front. Mol. Biosci.

View full text Add to dashboard Cite

Hereditary spastic paraplegias (HSPs) are genetically heterogeneous conditions caused by the progressive dying back of the longest axons in the central nervous system, the corticospinal axons. A wealth of data in the last decade has unraveled disturbances of lipid droplet (LD) biogenesis, maturation, turnover and contact sites in cellular and animal models with perturbed expression and function of HSP proteins. As ubiquitous organelles that segregate neutral lipid into a phospholipid monolayer, LDs are at the cross-road of several processes including lipid metabolism and trafficking, energy homeostasis, and stress signaling cascades. However, their role in brain cells, especially in neurons remains enigmatic. Here, we review experimental findings linking LD abnormalities to defective function of proteins encoded by HSP genes, and discuss arising questions in the context of the pathogenesis of HSP.

show abstract

Seipin-Mediated Contacts as Gatekeepers of Lipid Flux at the Endoplasmic Reticulum–Lipid Droplet Nexus

Cited by 15 publications

References 137 publications

Seipin localizes at endoplasmic-reticulum-mitochondria contact sites to control mitochondrial calcium import and metabolism in adipocytes

Seipin localizes at endoplasmic-reticulum-mitochondria contact sites to control mitochondrial calcium import and metabolism in adipocytes

Seipin transmembrane segments critically function in triglyceride nucleation and lipid droplet budding from the membrane

Lipid Droplets in the Pathogenesis of Hereditary Spastic Paraplegia

Contact Info

Product

Resources

About