Engineering Erg10 Thiolase from Saccharomyces cerevisiae as a Synthetic Toolkit for the Production of Branched-Chain Alcohols.

Thiolases catalyze the condensation of acyl-CoA thioesters through the Claisen condensation reaction. The best described enzymes usually yield linear condensation products. Using a combined computational/experimental approach, and guided by structural information, we have studied the potential of thiolases to synthesize branched compounds.

Mitochondrial uncoupling proteins: new perspectives for evolutionary ecologists.

Reactive oxygen species (ROS)-induced damage on host cells and molecules has been considered the most likely proximal mechanism responsible for the age-related decline in organismal performance. Organisms have two possible ways to reduce the negative effect of ROS: disposing of effective antioxidant defenses and minimizing ROS production. The unbalance between the amount of ROS produced and the availability of antioxidant defenses determines the intensity of so-called oxidative stress.

Adaptative metabolic response of human colonic epithelial cells to the adverse effects of the luminal compound sulfide.

Hydrogen sulfide (H(2)S), a bacterial metabolite present in the lumen of the large intestine, is able to exert deleterious effects on the colonic epithelium. The mechanisms involved are still poorly understood, the reported effect of sulfide being its capacity to reduce n-butyrate beta-oxidation in colonocytes. In this work, we studied both the acute effect of the sodium salt of H(2)S on human colonic epithelial cell metabolism and the adaptative response of these cells to the pre-treatment with this agent.

Avian uncoupling protein expressed in yeast mitochondria prevents endogenous free radical damage.

The longevity of birds is surprising since they exhibit high metabolic rates and elevated blood sugar levels compared with mammals of the same body size, which presumably expose them to higher rates of free oxygen radical production, which is implicated in accelerated senescence. Uncoupling proteins (UCPs) are transporters of the inner mitochondrial membrane and their physiological activity is still a subject of debate. Avian UCP was found in birds but data on its activity are scarce.

A new renal mitochondrial carrier, KMCP1, is up-regulated during tubular cell regeneration and induction of antioxidant enzymes.

The mitochondrial carrier family transports a variety of metabolites across the inner mitochondrial membrane. We identified and cloned a new member of this family, KMCP1 (kidney mitochondrial carrier protein-1), that is highly homologous to the previously identified protein BMCP1 (brain mitochondrial carrier protein-1). Western blotting and in situ experiments showed that this carrier is expressed predominantly within the kidney cortex in the proximal and distal tubules.

Mitochondrial uncoupling protein 1 expressed in the heart of transgenic mice protects against ischemic-reperfusion damage.

Background: Mitochondrial respiration is the main source of energy in aerobic animal cells and is adapted to the energy demand by respiratory coupling. Uncoupling proteins (UCPs) perturb respiratory coupling by inducing a proton leak through the mitochondrial inner membrane. Although this could lead to deleterious energy waste, it may prevent the production of oxygen radicals when the rate of phosphorylation of ADP into ATP is low, whereas oxygen and substrate availability to mitochondria is high.

High level of uncoupling protein 1 expression in muscle of transgenic mice selectively affects muscles at rest and decreases their IIb fiber content.

The mitochondrial uncoupling protein of brown adipose tissue (UCP1) was expressed in skeletal muscle and heart of transgenic mice at levels comparable with the amount found in brown adipose tissue mitochondria. These transgenic mice have a lower body weight, and when related to body weight, food intake and energy expenditure are increased. A specific reduction of muscle mass was observed but varied according to the contractile activity of muscles.

No evidence for a basal, retinoic, or superoxide-induced uncoupling activity of the uncoupling protein 2 present in spleen or lung mitochondria.

The phenotypes observed in mice whose uncoupling protein (Ucp2) gene had been invalidated by homologous recombination (Ucp2(-/-) mice) are consistent with an increase in mitochondrial membrane potential in macrophages and pancreatic beta cells. This could support an uncoupling (proton transport) activity of UCP2 in the inner mitochondrial membrane in vivo. We used mitochondria from lung or spleen, the two organs expressing the highest level of UCP2, to compare the proton leak of the mitochondrial inner membrane of wild-type and Ucp2(-/-) mice.