Adipogenin Dictates Adipose Tissue Expansion by Facilitating the Assembly of a Dodecameric Seipin Complex.

Adipogenin (Adig) is an evolutionarily conserved microprotein and is highly expressed in adipose tissues and testis. Here, we identify Adig as a critical regulator for lipid droplet formation in adipocytes. We determine that Adig interacts directly with seipin, leading to the formation of a rigid complex.

Fatty Acyl Coenzyme A Synthetase Fat1p Regulates Vacuolar Structure and Stationary-Phase Lipophagy in Saccharomyces cerevisiae.

During yeast stationary phase, a single spherical vacuole (lysosome) is created by the fusion of several small ones. Moreover, the vacuolar membrane is reconstructed into two distinct microdomains. Little is known, however, about how cells maintain vacuolar shape or regulate their microdomains.

Seipin forms a flexible cage at lipid droplet formation sites.

Lipid droplets (LDs) form in the endoplasmic reticulum by phase separation of neutral lipids. This process is facilitated by the seipin protein complex, which consists of a ring of seipin monomers, with a yet unclear function. Here, we report a structure of S.

Seipin: harvesting fat and keeping adipocytes healthy.

Seipin is a key protein in the assembly of cytoplasmic lipid droplets (cLDs) and their maintenance at endoplasmic reticulum (ER)-LD junctions; the absence of seipin results in generalized lipodystrophy. How seipin mediates LD dynamics and prevents lipodystrophy are not well understood. New evidence suggests that seipin attracts triglyceride monomers from the ER to sites of droplet formation.

Building the lipid droplet assembly complex.

In this issue, Choudhary et al. (2020. J.

LDAF1 Holds the Key to Seipin Function.

Seipin is an ER protein important for the assembly of cytoplasmic lipid droplets. In this issue of Developmental Cell, Chung et al. (2019) show that a stable seipin-binding protein, LDAF1/promethin, functions with seipin by attracting triacylglycerol and then allowing this lipid to accumulate and partition into nascent droplets.

Spatial compartmentalization of lipid droplet biogenesis.

Lipid droplets (LDs) are ubiquitous organelles that store metabolic energy in the form of neutral lipids (typically triacylglycerols and steryl esters). Beyond being inert energy storage compartments, LDs are dynamic organelles that participate in numerous essential metabolic functions. Cells generate LDs de novo from distinct sub-regions at the endoplasmic reticulum (ER), but what determines sites of LD formation remains a key unanswered question.

The assembly of lipid droplets and their roles in challenged cells.

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The assembly of lipid droplets and their roles in challenged cells.

Cytoplasmic lipid droplets are important organelles in nearly every eukaryotic and some prokaryotic cells. Storing and providing energy is their main function, but they do not work in isolation. They respond to stimuli initiated either on the cell surface or in the cytoplasm as conditions change.

Understanding the Lipid Droplet Proteome and Protein Targeting.

Reporting in this issue of Developmental Cell, Bersuker et al. (2018) adapt APEX technology to lipid droplets for a more accurate view of the droplet proteome and Prévost et al. (2018) provide important insights into the basis of droplet protein targeting that altogether extend the understanding of this organelle.

The collaborative work of droplet assembly.

Three proteins have been implicated in the assembly of cytoplasmic lipid droplets: seipin, FIT2, and perilipin. This review examines the current theories of seipin function as well as the evidence for the involvement of all three proteins in droplet biogenesis, and ends with a proposal of how they collaborate to regulate the formation of droplets. This article is part of a Special Issue entitled: Recent Advances in Lipid Droplet Biology edited by Rosalind Coleman and Matthijs Hesselink.

Dissecting seipin function: the localized accumulation of phosphatidic acid at ER/LD junctions in the absence of seipin is suppressed by Sei1p(ΔNterm) only in combination with Ldb16p.

Background: Seipin is required for the correct assembly of cytoplasmic lipid droplets. In the absence of the yeast seipin homolog Sei1p (formerly Fld1p), droplets are slow to bud from the endoplasmic reticulum, lack the normal component of proteins on their surface, are highly heterogeneous in size and shape, often bud into the nucleus, and promote local proliferation of the endoplasmic reticulum in which they become tangled. But the mechanism by which seipin catalyzes lipid droplet formation is still uncertain.

Arabidopsis SEIPIN Proteins Modulate Triacylglycerol Accumulation and Influence Lipid Droplet Proliferation.

The lipodystrophy protein SEIPIN is important for lipid droplet (LD) biogenesis in human and yeast cells. In contrast with the single SEIPIN genes in humans and yeast, there are three SEIPIN homologs in Arabidopsis thaliana, designated SEIPIN1, SEIPIN2, and SEIPIN3. Essentially nothing is known about the functions of SEIPIN homologs in plants.

The lipid droplet-a well-connected organelle.

Our knowledge of inter-organellar communication has grown exponentially in recent years. This review focuses on the interactions that cytoplasmic lipid droplets have with other organelles. Twenty-five years ago droplets were considered simply particles of coalesced fat.

The life cycle of lipid droplets.

Proteomic studies have revealed many potential functions of cytoplasmic lipid droplets, and recent activity has confirmed that these bona fide organelles are central not only for lipid storage and metabolism, but for development, immunity, and pathogenesis by several microbes. There has been a burst of recent activity on the assembly, maintenance and turnover of lipid droplets that reveals fresh insights. This review summarizes several novel findings in initiation of lipid droplet assembly, protein targeting, droplet fusion, and turnover of droplets through lipophagy.

Seipin performs dissectible functions in promoting lipid droplet biogenesis and regulating droplet morphology.

Seipin is necessary for both adipogenesis and lipid droplet (LD) organization in nonadipose tissues; however, its molecular function is incompletely understood. Phenotypes in the seipin-null mutant of Saccharomyces cerevisiae include aberrant droplet morphology (endoplasmic reticulum-droplet clusters and size heterogeneity) and sensitivity of droplet size to changes in phospholipid synthesis. It has not been clear, however, whether seipin acts in initiation of droplet synthesis or at a later step.

Seipin: from human disease to molecular mechanism.

The most-severe form of congenital generalized lipodystrophy (CGL) is caused by mutations in BSCL2/seipin. Seipin is a homo-oligomeric integral membrane protein in the endoplasmic reticulum that concentrates at junctions with cytoplasmic lipid droplets (LDs). While null mutations in seipin are responsible for lipodystrophy, dominant mutations cause peripheral neuropathy and other nervous system pathologies.

Nuclear envelope phosphatase 1-regulatory subunit 1 (formerly TMEM188) is the metazoan Spo7p ortholog and functions in the lipin activation pathway.

Lipin-1 catalyzes the formation of diacylglycerol from phosphatidic acid. Lipin-1 mutations cause lipodystrophy in mice and acute myopathy in humans. It is heavily phosphorylated, and the yeast ortholog Pah1p becomes membrane-associated and active upon dephosphorylation by the Nem1p-Spo7p membrane complex.

The yeast lipin orthologue Pah1p is important for biogenesis of lipid droplets.

Lipins are phosphatidate phosphatases that generate diacylglycerol (DAG). In this study, we report that yeast lipin, Pah1p, controls the formation of cytosolic lipid droplets. Disruption of PAH1 resulted in a 63% decrease in droplet number, although total neutral lipid levels did not change.

Seipin is a discrete homooligomer.

Seipin is a transmembrane protein that resides in the endoplasmic reticulum and concentrates at junctions between the ER and cytosolic lipid droplets. Mutations in the human seipin gene, including the missense mutation A212P, lead to congenital generalized lipodystrophy (CGL), characterized by the lack of normal adipose tissue and accumulation of fat in liver and muscles. In both yeast and CGL patient fibroblasts, seipin is required for normal lipid droplet morphology; in its absence droplets appear to bud abnormally from the ER.

Demonstrated and inferred metabolism associated with cytosolic lipid droplets.

Cytosolic lipid droplets were considered until recently to be rather inert particles of stored neutral lipid. Largely through proteomics is it now known that droplets are dynamic organelles and that they participate in several important metabolic reactions as well as trafficking and interorganellar communication. In this review, the role of droplets in metabolism in the yeast Saccharomyces cerevisiae, the fly Drosophila melanogaster, and several mammalian sources are discussed, particularly focusing on those reactions shared by these organisms.