RESUMEN
Mitochondria are known as the powerhouse of the cell. Dysfunction of mitochondria homeostasis induces the mitochondrial unfolded protein response (UPRmt), altering cellular metabolism. How cells sense the UPRmt to rewire metabolism is largely unknown. Here, we show that inactivation of either the citric/tricarboxylic acid (TCA) cycle enzymes aco-2 or idha-1, which encode aconitase and isocitrate dehydrogenase respectively, leads to citrate accumulation. In Caenorhabditis elegans, both in vitro and in vivo, citrate accumulation consequently triggers the UPRmt and also promotes lipid accumulation. The transcription factor DVE-1 binds to the promoter of the nuclear hormone receptor nhr-80 to transactivate its expression. NHR-80 then upregulates lipogenesis and lipid accumulation, shifting excess citrate for use in lipogenesis and for storage as triacylglycerol in lipid droplets. Inactivation of DVE-1 or NHR-80 fully abolishes the citrate-induced lipid accumulation. Therefore, our work uncovers a DVE-1-NHR-80-lipogenesis axis linking the transmission of the mitochondrial stress signal to lipid metabolism.
Asunto(s)
Proteínas de Caenorhabditis elegans/metabolismo , Ácido Cítrico/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Respuesta de Proteína Desplegada/fisiología , Animales , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/fisiología , Expresión Génica/genética , Regulación de la Expresión Génica/genética , Homeostasis , Metabolismo de los Lípidos/fisiología , Lípidos/fisiología , Mitocondrias/metabolismo , Receptores Citoplasmáticos y Nucleares/fisiología , Transducción de Señal , Factores de Transcripción/metabolismoRESUMEN
In eukaryote cells, lipid droplets (LDs) are key intracellular organelles that dynamically regulate cellular energy homeostasis. LDs originate from the ER and continuously contact the ER during their growth. How the ER affects LD growth is largely unknown. Here, we show that RNAi knockdown of acs-1, encoding an acyl-CoA synthetase required for the biosynthesis of monomethyl branched-chain fatty acids C15iso and C17iso, remarkably prevented LD growth in Caenorhabditis elegans. Dietary C17iso, or complex lipids with C17iso including phosphatidylcholine, phosphatidylethanolamine, and triacylglycerol, could fully restore the LD growth in the acs-1RNAi worms. Mechanistically, C17iso may incorporate into phospholipids to ensure the membrane integrity of the ER so as to maintain the function of ER-resident enzymes such as SCD/stearoyl-CoA desaturase and DGAT2/diacylglycerol acyltransferase for appropriate lipid synthesis and LD growth. Collectively, our work uncovers a unique fatty acid, C17iso, as the side chain of phospholipids for determining the ER homeostasis for LD growth in an intact organism, C. elegans.
Asunto(s)
Retículo Endoplásmico/metabolismo , Ácidos Grasos/metabolismo , Gotas Lipídicas/metabolismo , Animales , Caenorhabditis elegans/metabolismo , Homeostasis/fisiología , Metabolismo de los Lípidos/fisiología , Membranas/metabolismo , Fosfolípidos/metabolismo , Interferencia de ARN/fisiologíaRESUMEN
Surveys of Toxoplasma gondii infection in animals have been reported in Yunnan province, southwestern China. However, limited information is available regarding the epidemiology of T. gondii infection among persons participated in health screening in Yunnan. From January 2014 to December 2016, a large-scale and cross-sectional serological survey was conducted to reveal the seroprevalence of T. gondii infection in persons participated in health screening in three major hospitals. A total of 64,533 serum samples were collected and anti-T. gondii antibodies were examined by commercially available enzyme-linked immunosorbent assay kits. The total seroprevalence of T. gondii infection was 6.67% (4306/64,533). Of these, 3721 persons (5.77%, 3721/64,533) were positive for Immunoglobulin G (IgG) only, 473 persons (0.73%, 473/64,533) were positive for Immunoglobulin M (IgM) only, and 112 persons (0.17%, 112/64,533) were positive for both IgG and IgM. Female seroprevalence (6.83%, 3167/46,389) was higher than male (6.28%, 1139/18,144). The highest seroprevalence of T. gondii infection was found in the age range of 41-50 years (10.60%, 228/2150) (p < 0.001). The seroprevalence in 2014, 2015, and 2016 were 6.39% (1083/16,946), 6.24% (1261/20,201), and 7.16% (1962/27,386), respectively. The results showed that T. gondii infection is common in persons participated in health screening in Yunnan province, which has significant public health concern. Thus, improved integrated measures should be executed to prevent and control T. gondii infection humans and animals in Yunnan province.