Nuclear translocation ability of Lipin differentially affects gene expression and survival in fed and fasting Drosophila
| Autor: | Jason Ortega, Judah Scott, Michael Lehmann, Quiyu Chen, Xeniya V. Kofler, Stephanie E. Hood |
|---|---|
| Přispěvatelé: | University of Zurich, Lehmann, Michael |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
1303 Biochemistry Nuclear gene Mutant Active Transport Cell Nucleus feeding behavior Chromosomal translocation QD415-436 580 Plants (Botany) 030204 cardiovascular system & hematology Biology Biochemistry immune response 1307 Cell Biology 03 medical and health sciences 0302 clinical medicine Endocrinology 10126 Department of Plant and Microbial Biology Gene expression energy metabolism medicine Animals Organic Chemicals 10211 Zurich-Basel Plant Science Center Gene Research Articles Cell Nucleus metabolic health Fasting Cell Biology Phosphatidate phosphatase Survival Analysis 1310 Endocrinology Cell biology genomic starvation response Cell nucleus 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Drosophila Nuclear localization sequence |
| Zdroj: | Journal of Lipid Research, Vol 61, Iss 12, Pp 1720-1732 (2020) J Lipid Res |
| ISSN: | 0022-2275 |
| Popis: | Lipins are eukaryotic proteins with functions in lipid synthesis and the homeostatic control of energy balance. They execute these functions by acting as phosphatidate phosphatase enzymes in the cytoplasm and by changing gene expression after translocation into the cell nucleus, in particular under fasting conditions. Here, we asked whether nuclear translocation and the enzymatic activity of Drosophila Lipin serve essential functions and how gene expression changes, under both fed and fasting conditions, when nuclear translocation is impaired. To address these questions, we created a Lipin null mutant, a mutant expressing Lipin lacking a nuclear localization signal (Lipin(ΔNLS)), and a mutant expressing enzymatically dead Lipin. Our data support the conclusion that the enzymatic but not nuclear gene regulatory activity of Lipin is essential for survival. Notably, adult Lipin(ΔNLS) flies were not only viable but also exhibited improved life expectancy. In contrast, they were highly susceptible to starvation. Both the improved life expectancy in the fed state and the decreased survival in the fasting state correlated with changes in metabolic gene expression. Moreover, increased life expectancy of fed flies was associated with a decreased metabolic rate. Interestingly, in addition to metabolic genes, genes involved in feeding behavior and the immune response were misregulated in Lipin(ΔNLS) flies. Altogether, our data suggest that the nuclear activity of Lipin influences the genomic response to nutrient availability with effects on life expectancy and starvation resistance. Thus, nutritional or therapeutic approaches that aim at lowering nuclear translocation of lipins in humans may be worth exploring. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|