REDOX LIPIDOMICS OF PROGRAMMED CELL DEATH SIGNALING.

Abstract

From the very early stages since the emergence of life on our planet, phospholipids played a very essential role by fulfilling two major functions: 1) as structural building blocks of membranes, and 2) as communication signals. Among many different mechanisms, oxygenation of polyunsaturated lipids played an essential role in coordinating numerous metabolic reactions and pathways, including death programs. Cells overpowered by viruses or bacterial pathogens or overburdened with genotoxic material are destined to die through one of the strictly coordinated death pathways. As several new programs of cell death have been discovered, they turned to be closely interconnected and failure of one of them inevitably triggers another one such the ultimate goal – elimination of the damaged cell representing high risk for the multi-cellular community – is achieved. This paramount role of oxygenated polyunsaturated lipids in regulation is also associated with a risk of their involvement in aberrant injury reactions due to lipid peroxidation and the production of secondary reactive lipid electrophiles. In this talk, we will discuss how redox lipidomics discovered specific predictive oxygenated phospholipid biomarkers acting as signals in two important death programs – apoptosis and ferroptosis. We will present mechanistic data describing the enzymatic machinery that generates highly specific oxygenated phospholipids – cardiolipins and phosphatidylethanolamines in apoptosis and ferroptosis, respectively.