Nuclear-Lipid-Droplet Proteome

VES LOSADA, ANA

Online Meeting

Otro; International Webinar on Cancer Research and Oncology; 2021

Scientific Meditech and the Organizing Committee of Cancer Webinar

Nuclear-lipid droplets (nLD)?a dynamic cellular organelle that stores neutral lipids, within the nucleus of eukaryotic cells?consists of a hydrophobic triacylglycerol ?cholesterol-ester core enriched in oleic acid (OA) surrounded by a monolayer of polar lipids, cholesterol, and proteins. nLD are probably involved in nuclear-lipid homeostasis serving as an endonuclear buffer provides or incorporates lipids and proteins participating in signaling pathways, as transcription factors and enzymes of lipid metabolism and nuclear processes. In the present work, we analyzed the nLD proteome and hypothesized that nLD-monolayer proteins could be involved in processes similar as the ones occurring in the cLD including lipid metabolism and other cellular functions. We evaluated the rat-liver?nLD proteome under physiological and nonpathological conditions by GeLC-MS2. Since isolated nLD are highly diluted, a protein-concentrating isolation protocol was designed. Thirty-five proteins were identified within the functional categories: cytoskeleton and structural, transcription and translation, histones, protein-folding and posttranslational modification, cellular proliferation and/or cancer, lipid metabolism, and transport. Purified nLD contained an enzyme from the lipid-metabolism pathway, carboxylesterase 1d (Ces1d/Ces3). By in-silico analyses rat Ces1d/Ces3 secondary and tertiary structure predicted would be equivalent to human CES1.In conclusion, the results reported here are the first describing the nLD proteome. The approach revealed a wide diversity in cellular function of the proteins, what indicated that the nLD are directly or indirectly participating in those cellular processes; with the carboxylesterase Ces1d/Ces3 protein, for its part, being involved in cellular LD-population dynamics. Moreover, the enzymatic activity of LD carboxylesterase could generate molecules in situ that in addition to being oxidized could constitute lipidic second messengers to regulate the nuclear- and/or cellular-lipid homeostasis.