RESUMO
The lipid droplet (LD) is a unique multi-functional organelle that contains a neutral lipid core covered with a phospholipid monolayer membrane. The LDs have been found in almost all organisms from bacteria to humans with similar shape. Several conserved functions of LDs have been revealed by recent studies, including lipid metabolism and trafficking, as well as nucleic acid binding and protection. We summarized these findings and proposed a hypothesis that the LD is a conserved organelle.
Assuntos
Animais , Humanos , Bactérias , Metabolismo , Evolução Biológica , Ésteres do Colesterol , Metabolismo , Gotículas Lipídicas , Química , Metabolismo , Metabolismo dos Lipídeos , Genética , Ácidos Nucleicos , Metabolismo , Fatores de Iniciação de Peptídeos , Química , Metabolismo , Ligação Proteica , Proteínas de Ligação a RNA , Química , Metabolismo , Subunidades Ribossômicas , Química , Metabolismo , Triglicerídeos , MetabolismoRESUMO
Non-alcoholic fatty liver disease (NAFLD) is an epidemic metabolic condition driven by an underlying lipid homeostasis disorder. The lipid droplet (LD), the main organelle involved in neutral lipid storage and hydrolysis, is a potential target for NAFLD therapeutic treatment. In this review, we summarize recent progress elucidating the connections between LD-associated proteins and NAFLD found by genome-wide association studies (GWAS), genomic and proteomic studies. Finally, we discuss a possible mechanism by which the protein 17β-hydroxysteroid dehydrogenase 13 (17β-HSD13) may promote the development of NAFLD.
Assuntos
Animais , Humanos , 17-Hidroxiesteroide Desidrogenases , Genética , Metabolismo , Estudo de Associação Genômica Ampla , Genômica , Gotículas Lipídicas , Metabolismo , Metabolismo dos Lipídeos , Genética , Hepatopatia Gordurosa não Alcoólica , Genética , Metabolismo , ProteômicaRESUMO
Lipid droplets, which are conserved across almost all species, are cytoplasmic organelles used to store neutral lipids. Identification of lipid droplet regulators will be conducive to resolving obesity and other fat-associated diseases. In this paper, we selected 11 candidates that might be associated with lipid metabolism in Caenorhabditis elegans. Using a BODIPY 493/503-based flow cytometry screen, 6 negative and 3 positive regulators of fat content were identified. We selected one negative regulator of lipid content, C13C4.5, for future study. C13C4.5 was mainly expressed in the worm intestine. We found that this gene was important for maintaining the metabolism of lipid droplets. Biochemical results revealed that 50% of triacylglycerol (TAG) was lost in C13C4.5 knockout worms. Stimulated Raman scattering (SRS) signals in C13C4.5 mutants showed only 49.6% of the fat content in the proximal intestinal region and 86.3% in the distal intestinal region compared with wild type animals. The mean values of lipid droplet size and intensity in C13C4.5 knockout animals were found to be significantly decreased compared with those in wild type worms. The LMP-1-labeled membrane structures in worm intestines were also enlarged in C13C4.5 mutant animals. Finally, fertility defects were found in C13C4.5(ok2087) mutants. Taken together, these results indicate that C13C4.5 may regulate the fertility of C. elegans by changing the size and fat content of lipid droplets by interfering with lysosomal morphology and function.
Assuntos
Animais , Humanos , Evolução Biológica , Caenorhabditis elegans , Genética , Metabolismo , Proteínas de Caenorhabditis elegans , Genética , Metabolismo , Fertilidade , Citometria de Fluxo , Técnicas de Inativação de Genes , Metabolismo dos Lipídeos , Genética , Lisossomos , Genética , Metabolismo , Proteínas de Membrana , Genética , Redes e Vias Metabólicas , Genética , Triglicerídeos , MetabolismoRESUMO
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.
Assuntos
Animais , Ratos , Linhagem Celular , Teste de Complementação Genética , Metabolismo dos Lipídeos , Lipídeos , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Mitocôndrias , Metabolismo , Células Musculares , Metabolismo , Músculo Esquelético , Biologia Celular , Metabolismo , Proteínas Oncogênicas , Genética , Metabolismo , Peroxissomos , Metabolismo , Plasmídeos , Ligação Proteica , Mapeamento de Interação de Proteínas , Métodos , Proteínas Recombinantes de Fusão , Genética , Metabolismo , Saccharomyces cerevisiae , Fatores de Transcrição , Genética , Metabolismo , Transformação GenéticaRESUMO
Caenorhabditis elegans hid-1 gene was first identified in a screen for mutants with a high-temperature-induced dauer formation (Hid) phenotype. Despite the fact that the hid-1 gene encodes a novel protein (HID-1) which is highly conserved from Caenorhabditis elegans to mammals, the domain structure, subcellular localization, and exact function of HID-1 remain unknown. Previous studies and various bioinformatic softwares predicted that HID-1 contained many transmembrane domains but no known functional domain. In this study, we revealed that mammalian HID-1 localized to the medial- and trans- Golgi apparatus as well as the cytosol, and the localization was sensitive to brefeldin A treatment. Next, we demonstrated that HID-1 was a peripheral membrane protein and dynamically shuttled between the Golgi apparatus and the cytosol. Finally, we verified that a conserved N-terminal myristoylation site was required for HID-1 binding to the Golgi apparatus. We propose that HID-1 is probably involved in the intracellular trafficking within the Golgi region.