Fatty acid metabolism, innate immune response and mitochondrial fitness are known to be interconnected. As we identified these signatures to be differentially regulated in isogenic immortalized fibroblast cell lines that are either telomerase- or ALT-positive, we investigated whether lipid metabolism, cytoplasmic telomeric DNA species and/or mitochondrial DNA release were involved in the observed differential induction of the innate immune response. In addition, we found that the telomere maintenance mechanism strongly modulates yet another aspect of cellular metabolism: the resistance of cells to ferroptosis, a cell death mechanism induced by the peroxidation of membrane phospholipids. Importantly, we confirmed our observations in telomerase-positive and ALT-positive sarcoma cell lines. Together, these data bring new light on the increasing connections between telomeres, telomere maintenance mechanisms and cellular metabolism.
Derumier et al. (Mon,) studied this question.