Probing the unconventional functions of lipins in the nucleus

Lipins catalyse a key step in lipid metabolism that is essential for triacylglycerol production in the endoplasmic reticulum. Triacylglycerol is the major cellular energy storage molecule and disruption of its normal metabolism underpins type 2 diabetes and obesity. Surprisingly, lipins also have a distinct pool in the nucleus of many cell types. How their cytoplasmic lipid metabolic roles are coordinated with their largely uncharacterised nuclear functions is unknown.

We have generated lipin mutants that retain their activity as lipid metabolic enzymes but fail to enter the nucleus. Our aim is to use these mutants to define the functional and physical partners of the yeast lipin Pah1 in the nucleus. This is the first step of a longer-term plan to define the dual function of the lipin family of enzymes. The specific goals of the proposed work are to identify the complete set of genes that are transcriptionally regulated by the nuclear pool of Pah1 and determine whether this regulation is direct or indirect. We will also Identify the genome-wide map of chromatin-bound Pah1 genes and define which factors are required for the function of Pah1 in the nucleus.