MedUni Wien RESEARCHER OF THE MONTH October 2019
The Inner Nuclear Membrane Is a Metabolically Active Territory that Generates Nuclear Lipid Droplets.
The inner nuclear membrane (INM) encases the genome and is fused with the outer nuclear membrane (ONM) to form the nuclear envelope. The ONM is contiguous with the endoplasmic reticulum (ER), the main site of phospholipid synthesis. In contrast to the ER and ONM, evidence for a metabolic activity of the INM has been lacking. The work by Romanauska&Köhler shows that the INM is not merely a remote, spatially isolated province that is dependent on lipid supplies from the ER. Instead, the INM as a territory with its own lipid metabolism and striking metabolic adaptability. Authors showed that cells target lipid metabolism enzymes to the INM that can promote lipid storage. Lipid storage involves the synthesis of nuclear lipid droplets (nLDs) from the INM and is characterized by lipid exchange through Seipin-dependent membrane bridges. Mutations in Seipin are associated with severe congenital lipodystrophy. This study identified the genetic circuit for nuclear lipid droplet synthesis and a role of these organelles in regulating this circuit by sequestration of a transcription factor. The physiologic importance of lipid storage at the INM is underscored by the fact that a surplus of fatty acids induces nLD formation. These findings by Romanauska& Köhler suggest a link between INM metabolism and genome regulation and have potential relevance for human lipodystrophy. This opens avenues for investigating the function of nuclear energy storage, as well as links between INM lipid metabolism and gene regulation.
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