Isotope-reinforced polyunsaturated fatty acids protect yeast cells from oxidative stress
Autoxidation of polyunsaturated fatty acids (PUFAs)1 , or lipid peroxidation, is a consequence of life in an oxygen-enriched atmosphere. This process is detrimental to the cell and has been linked to age-related degenerative diseases and is associated with apoptosis. However, PUFAs such as linoleic acid (Lin; 18:2, n–6) and α-linolenic acid (αLnn; 18:3, n–3) are essential fatty acids for humans and many animals and are important constituents of membranes. Mitochondrial membranes are particularly enriched in PUFAs, which are present in 80% of the total phospholipids. PUFAs are vital for optimal function of respiratory electron transport and oxidative phosphorylation, but are easily damaged, reacting with reactive oxygen species (ROS) through a chain reaction mechanism. In addition to deteriorating membrane fluidity, oxidized PUFAs relay oxidative damage to other biomolecules, most notably proteins and DNA [7], through reactive carbonyl compounds such as malondialdehyde (MDA), 4-hydroxynonenal (HNE), and 4-hydroxyhexenal (HHE). HNE and HHE are both small-molecule 4-hydroxyalkenals, but have profound differences in solubility and react distinctly with phospholipid and protein targets