Biogenesis of mitochondria 20 the effects of altered membrane lipid composition on mitochondrial oxidative phosphorylation inSaccharomyces cerevisiae

Abstract

Abstract1. The lipid composition of mitochondria isolated from a fatty acid desaturase mutant of Saccharomyces cerevisiae may be extensively manipulated by growing the organism on defined supplements of unsaturated fatty acid (UFA).2. The fatty acid composition of the mitochondrial lipids closely follows that of the whole ceils from which the mitochondria are isolated. UFA-depleted mitochondria contain normal levels of sterols, neutral lipids and total phospholipids, but have much lower levels of phosphatidyl inositides.3. UFA-depleted mitochondria possess a full complement of cytochromes, oxidase both NAD-linked and flavoprotein-linked substrates at normal rates, and have levels of succinate and malate dehydrogenases similar to those of UFA-supplemented mitochondria. However, UFA-depletion has a marked effect on the ability ofcytochrome c to reactivate the NADH oxidase activity of cytochrome c-depleted mitochondria.4. The efficiency of oxidative phosphorylation decreases progressively with the UFA content of the mitochondria, and oxidative phosphorylation is completely lost in mitochondria containing approximately 20% UFA. The incorporation of UFA into the lipids of UFA-depleted mitochondria in vivo resultsin a recoupling of oxidative phosphorylation. Recoupling is insensitive to both chloramphenicol and cycloheximide, indicating that all the proteins necessary for oxidative phosphorylation are present in UFA-depleted mitochondria, and that the less of oxidative phosphorylation is a purely lipid lesion.6. ATPase activity is apparently unaffected by UFA-depletion, but 32pi-ATP exchange activity is lost in mitochondria which have been extensively depleted in UFA.7. Valinomycin stimulates the respiration of UFA-supplemented mitochondria in media containing potassium, but has no effect on the respiration of UFA-depleted mitochondria, suggesting that active transport of potassium is lost as a result of UFA-depletion.

Evolution of energy metabolism. Proton permeability of the inner membrane of liver mitochondria is greater in a mammal than in a reptile

“…The second potential mechanism involves the nature of the fatty acid side chains of the phospholipids of the mitochondrial membrane. Manipulation of yeast mitochondrial membrane fatty acids has been shown to result in changes in the proton permeability and phosphorylating ability (Haslam et al, 1971). We have shown here (Table 3) that there are substantial differences in the membrane fatty acids between lizard and rat mitochondria and suggest that these may be related to the increased proton permeability of the mammalian mitochondria.…”

Stress tolerance in a yeast lipid mutant: membrane lipids influence tolerance to heat and ethanol independently of heat shock proteins and trehalose

“…Furthermore, it has been shown in yeast, that membrane lipid composition is crucial for cell function. Studies using fatty acid auxotrophs of Saccharomyces cerevisiae, have demonstrated that mitochondria lose the ability to carry out oxidative phosphorylation when the level of unsaturated fatty acids falls below 20% (Haslam et al 1971(Haslam et al , 1973, a phenomenon directly related to decreased cytochrome content and respiratory competence (Watson et al 1975). Amino acid transport in yeast is also influenced by fatty acyl composition (Mishra and Prasad 1987) and membrane fluidity (Mishra and Prasad 1989).…”

Role of nitric oxide on mitochondrial biogenesis during the ovarian cycle

“…Epigenetic factors have been involved in mitochondrial biogenesis: the inhibition of oxidative phosphorylation in mitochondrial myopathies (27); the uncoupling of mitochondria by thyroid hormone (28)(29)(30); the modification of the mitochondrial membrane composition (31); and pharmacological products as Diazepam (32), induce mitochondrial proliferation.…”