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Nuclear translocation ability of Lipin differentially affects gene expression and survival in fed and fasting Drosophila

Hood, Stephanie E; Kofler, Xeniya V; Chen, Quiyu; Scott, Judah; Ortega, Jason; Lehmann, Michael (2020). Nuclear translocation ability of Lipin differentially affects gene expression and survival in fed and fasting Drosophila. Journal of Lipid Research, 61(12):1720-1732.

Abstract

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 (LipinΔNLS ), 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 LipinΔNLS 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 LipinΔNLS 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.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Plant and Microbial Biology
07 Faculty of Science > Zurich-Basel Plant Science Center
Dewey Decimal Classification:580 Plants (Botany)
Scopus Subject Areas:Life Sciences > Biochemistry
Life Sciences > Endocrinology
Life Sciences > Cell Biology
Uncontrolled Keywords:Cell Biology, Biochemistry, Endocrinology
Language:English
Date:1 December 2020
Deposited On:15 Jan 2021 16:03
Last Modified:24 Oct 2024 01:40
Publisher:American Society for Biochemistry and Molecular Biology
ISSN:0022-2275
OA Status:Hybrid
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1194/jlr.ra120001051
PubMed ID:32989002
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