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Isotope-reinforced polyunsaturated fatty acids protect yeast cells from oxidative stress

2010; Elsevier BV; Volume: 50; Issue: 1 Linguagem: Inglês

10.1016/j.freeradbiomed.2010.10.690

1873-4596

Shauna Hill, Kathleen Hirano, Vadim V. Shmanai, Beth N. Marbois, D. Vidović, Andrei V. Bekish, Bradley Kay, Vincent Tse, Jonathan Fine, Catherine F. Clarke, Mikhail S. Shchepinov,

Mitochondrial Function and Pathology

The facile abstraction of bis-allylic hydrogens from polyunsaturated fatty acids (PUFAs) is the hallmark chemistry responsible for initiation and propagation of autoxidation reactions. The products of these autoxidation reactions can form cross-links to other membrane components and damage proteins and nucleic acids. We report that PUFAs deuterated at bis-allylic sites are much more resistant to autoxidation reactions, because of the isotope effect. This is shown using coenzyme Q-deficient Saccharomyces cerevisiae coq mutants with defects in the biosynthesis of coenzyme Q (Q). Q functions in respiratory energy metabolism and also functions as a lipid-soluble antioxidant. Yeast coq mutants incubated in the presence of the PUFA α-linolenic or linoleic acid exhibit 99% loss of colony formation after 4 h, demonstrating a profound loss of viability. In contrast, coq mutants treated with monounsaturated oleic acid or with one of the deuterated PUFAs, 11,11-D2-linoleic or 11,11,14,14-D4-α-linolenic acid, retain viability similar to wild-type yeast. Deuterated PUFAs also confer protection to wild-type yeast subjected to heat stress. These results indicate that isotope-reinforced PUFAs are stabilized compared to standard PUFAs, and they protect coq mutants and wild-type yeast cells against the toxic effects of lipid autoxidation products. These findings suggest new approaches to controlling ROS-inflicted cellular damage and oxidative stress.