From telomere maintenance mechanism to lipid metabolism: exploring the impact of telomerase or alternative mechanism on PUFA metabolism in human fibroblast cells

Details

Supervisors

Decottignies, Anabelle ; Larondelle, Yvan

Faculty

Faculté des bioingénieurs

Degree label

Master [120] : bioingénieur en chimie et bioindustries, à finalité spécialisée

Abstract

Cellular immortality stands as a hallmark of cancer, achieved through mechanisms that maintain the length of chromosome ends, known as telomeres. Telomeres protect chromosome ends from being identified as double-strand breaks by DNA repair systems, preserving chromosomal integrity. As cells divide, telomeres shorten, eventually leading to cellular senescence and cell death. Two distinct telomere maintenance mechanisms exist. The first, most common, is the reactivation of telomerase (TEL), an enzyme that adds telomeric sequences to the pre-existing sequence. The second is the Alternative Lengthening of Telomeres (ALT) mechanism, relying on homologous recombination to elongate telomeres. The laboratory is comparing TEL+ and ALT+ cells to gain a better understanding of their mode of action and their impact on cellular metabolism. Through RNA sequencing, the laboratory detected differences between TEL+ and ALT+ cells in the expression levels of RNA associated with certain enzymes involved in lipid metabolism, particularly PUFAs. After confirming these candidates, an analysis of lipid composition revealed distinctions in polyunsaturated fatty acids (PUFAs) levels for neutral lipids and phospholipids, two of the lipid fractions. PUFAs are lipids playing essential roles in various processes such as membranes fluidity or inflammation regulation and are precursors of many bioactive molecules. Interested in the differences in neutral lipid composition, the laboratory also conducted quantification of lipid droplets, dynamic organelles primarily composed of these neutral lipids and playing significant roles in cellular metabolism. This master’s thesis raises the question of the role of telomerase reactivation in lipid metabolism. The results obtained during various manipulations suggest that telomerase could influence the levels of PUFAs in the cellular lipid composition. One hypothesis proposed in this work is that telomerase might enhance the cells' ability to assimilate lipids. Other questions are also raised, and some suggestions are made to attempt to address these inquiries.