Browse
Submit Data
Databases
API
Help

Dataset Information

17 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Trafficking of cholesterol from lipid droplets to mitochondria in bovine luteal cells: Acute control of progesterone synthesis.

ABSTRACT: The corpus luteum is a transient endocrine gland that synthesizes and secretes the steroid hormone, progesterone, which is vital for establishment and maintenance of pregnancy. Luteinizing hormone (LH) via activation of protein kinase A (PKA) acutely stimulates luteal progesterone synthesis via a complex process, converting cholesterol via a series of enzymatic reactions, into progesterone. Lipid droplets in steroidogenic luteal cells store cholesterol in the form of cholesterol esters, which are postulated to provide substrate for steroidogenesis. Early enzymatic studies showed that hormone sensitive lipase (HSL) hydrolyzes luteal cholesterol esters. In this study, we tested whether HSL is a critical mediator of the acute actions of LH on luteal progesterone production. Using LH-responsive bovine small luteal cells our results reveal that LH, forskolin, and 8-Br cAMP-induced PKA-dependent phosphorylation of HSL at Ser563 and Ser660, events known to promote HSL activity. Small molecule inhibition of HSL activity and siRNA-mediated knock down of HSL abrogated LH-induced progesterone production. Moreover, western blotting and confocal microscopy revealed that LH stimulates phosphorylation and translocation of HSL to lipid droplets. Furthermore, LH increased trafficking of cholesterol from the lipid droplets to the mitochondria, which was dependent on both PKA and HSL activation. Taken together, these findings identify a PKA/HSL signaling pathway in luteal cells in response to LH and demonstrate the dynamic relationship between PKA, HSL, and lipid droplets in luteal progesterone synthesis.

SUBMITTER: Plewes MR

PROVIDER: S-EPMC7868007 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Glycerolipid synthesis and lipid trafficking in plant mitochondria.

Project description:Lipid trafficking between mitochondria and other organelles is required for mitochondrial membrane biogenesis and signaling. This lipid exchange occurs by poorly understood nonvesicular mechanisms. In yeast and mammalian cells, this lipid exchange is thought to take place at contact sites between mitochondria and the ER or vacuolar membranes. Some proteins involved in the tethering between membranes or in the transfer of lipids in mitochondria have been identified. However, in plants, little is known about the synthesis of mitochondrial membranes. Mitochondrial membrane biogenesis is particularly important and noteworthy in plants as the lipid composition of mitochondrial membranes is dramatically changed during phosphate starvation and other stresses. This review focuses on the principal pathways involved in the synthesis of the most abundant mitochondrial glycerolipids in plants and the lipid trafficking that is required for plant mitochondria membrane biogenesis.

| S-EPMC6224293 | biostudies-literature

Interactomic study on interaction between lipid droplets and mitochondria.

Project description:An increasing body of evidence shows that the lipid droplet, a neutral lipid storage organelle, plays a role in lipid metabolism and energy homeostasis through its interaction with mitochondria. However, the cellular functions and molecular mechanisms of the interaction remain ambiguous. Here we present data from transmission electron microscopy, fluorescence imaging, and reconstitution assays, demonstrating that lipid droplets physically contact mitochondria in vivo and in vitro. Using a bimolecular fluorescence complementation assay in Saccharomyces cerevisiae, we generated an interactomic map of protein-protein contacts of lipid droplets with mitochondria and peroxisomes. The lipid droplet proteins Erg6 and Pet10 were found to be involved in 75% of the interactions detected. Interestingly, interactions between 3 pairs of lipid metabolic enzymes were detected. Collectively, these data demonstrate that lipid droplets make physical contacts with mitochondria and peroxisomes, and reveal specific molecular interactions that suggest active participation of lipid droplets in lipid metabolism in yeast.

| S-EPMC4875178 | biostudies-literature

DGAT enzymes are required for triacylglycerol synthesis and lipid droplets in adipocytes

Project description:Murine embryonic fibroblasts were isolated from WT and DGAT1,DGAT2-KO (D1D2KO) animals. mRNA was isolated from cells untreated (UNDIFF) or treated (DIFF) according to standard differentiation protocol for adipocytes (Harris, C, et al. JLR 2011). 12 Samples total: 3 biological replicates of 3 undifferentiated wild type and D1D2KO mice and 3 biological replicates of 3 differentiated wild type and D1D2KO mice.

2011-01-31 | E-GEOD-26624 | biostudies-arrayexpress

Lipid droplets and mitochondria are anchored during brown adipocyte differentiation.

Project description: Not available

| S-EPMC6881423 | biostudies-literature

Mitochondria Bound to Lipid Droplets: Where Mitochondrial Dynamics Regulate Lipid Storage and Utilization.

Project description:The isolation and biochemical characterization of lipid droplet (LD)-associated mitochondria revealed the capacity of the cell to produce and maintain distinct mitochondrial populations carrying disparate proteome and dissimilar capacities to oxidize fatty acids and pyruvate. With mitochondrial motility being a central parameter determining mitochondrial fusion, adherence to LDs provides a mechanism by which peridroplet mitochondria (PDM) remain segregated from cytoplasmic mitochondria (CM). The existence of metabolically distinct subpopulations provides an explanation for the capacity of mitochondria within the individual cell to be involved simultaneously in fatty acid oxidation and LD formation. The mechanisms that deploy mitochondria to the LD and the dysfunctions that result from unbalanced proportions of PDM and CM remain to be explored. Understanding the roles and regulation of mitochondrial tethering to LDs offers new points of intervention in metabolic diseases.

| S-EPMC6476311 | biostudies-literature

Translation inhibitors induce formation of cholesterol ester-rich lipid droplets.

Project description:Lipid droplets (LDs) in non-adipocytes contain triglycerides (TG) and cholesterol esters (CE) in variable ratios. TG-rich LDs are generated when unsaturated fatty acids are administered, but the conditions that induce CE-rich LD formation are less well characterized. In the present study, we found that protein translation inhibitors such as cycloheximide (CHX) induced generation of CE-rich LDs and that TIP47 (perilipin 3) was recruited to the LDs, although the expression of this protein was reduced drastically. Electron microscopy revealed that LDs formed in CHX-treated cells possess a distinct electron-dense rim that is not found in TG-rich LDs, whose formation is induced by oleic acid. CHX treatment caused upregulation of mTORC1, but the CHX-induced increase in CE-rich LDs occurred even when rapamycin or Torin1 was given along with CHX. Moreover, the increase in CE was seen in both wild-type and autophagy-deficient Atg5-null mouse embryonic fibroblasts, indicating that mTORC1 activation and suppression of autophagy are not necessary to induce the observed phenomenon. The results showed that translation inhibitors cause a significant change in the lipid ester composition of LDs by a mechanism independent of mTORC1 signaling and autophagy.

| S-EPMC3411751 | biostudies-literature

Progesterone vaginal ring for luteal support.

Project description:Progesterone supplementation is universally used and has been shown to be beneficial in supplementation of the luteal phase in IVF. There are multiple options and the most commonly used include intramuscular and vaginal progesterone. A progesterone vaginal ring is a novel system for luteal support with advantages of controlled release with less frequent dosing. This review examines options for progesterone luteal support focusing on the rationale for a progesterone vaginal ring. Pub-med search of the literature. A weekly vaginal ring, although not yet FDA approved, is an effective and safe alternative for luteal supplementation in IVF. Large prospective clinical trials are needed to determine the best protocols for replacement cycles.

| S-EPMC4342373 | biostudies-other

DGAT enzymes are required for triacylglycerol synthesis and lipid droplets in adipocytes

2011-01-31 | GSE26624 | GEO

Lipid Droplets Protect Aging Mitochondria and Thus Promote Lifespan in Yeast Cells.

Project description:Besides their role as a storage for neutral lipids and sterols, there is increasing evidence that lipid droplets (LDs) are involved in cellular detoxification. LDs are in close contact to a broad variety of organelles where protein- and lipid exchange is mediated. Mitochondria as a main driver of the aging process produce reactive oxygen species (ROS), which damage several cellular components. LDs as highly dynamic organelles mediate a potent detoxification mechanism by taking up toxic lipids and proteins. A stimulation of LDs induced by the simultaneously overexpression of Lro1p and Dga1p (both encoding acyltransferases) prolongs the chronological as well as the replicative lifespan of yeast cells. The increased number of LDs reduces mitochondrial fragmentation as well as mitochondrial ROS production, both phenotypes that are signs of aging. Strains with an altered LD content or morphology as in the sei1∆ or lro1∆ mutant lead to a reduced replicative lifespan. In a yeast strain defective for the LON protease Pim1p, which showed an enhanced ROS production, increased doubling time and an altered mitochondrial morphology, a LRO1 overexpression resulted in a partially reversion of this "premature aging" phenotype.

| S-EPMC8640092 | biostudies-literature

Correction to: Lipid droplets and mitochondria are anchored during brown adipocyte differentiation.

Project description: Not available

| S-EPMC8403092 | biostudies-literature