Ask yeast how to burn your fats: lessons learned from the metabolic adaptation to salt stress

[EN] Here, we review and update the recent advances in the metabolic control during the adaptive response of budding yeast to hyperosmotic and salt stress, which is one of the best understood signaling events at the molecular level. This environmental stress can be easily applied and hence has been exploited in the past to generate an impressively detailed and comprehensive model of cellular adaptation. It is clear now that this stress modulates a great number of different physiological functions of the cell, which altogether contribute to cellular survival and adaptation. Primary defense mechanisms are the massive induction of stress tolerance genes in the nucleus, the activation of cation transport at the plasma membrane, or the production and intracellular accumulation of osmolytes. At the same time and in a coordinated manner, the cell shuts down the expression of housekeeping genes, delays the progression of the cell cycle, inhibits genomic replication, and modulates translation efficiency to optimize the response and to avoid cellular damage. To this fascinating interplay of cellular functions directly regulated by the stress, we have to add yet another layer of control, which is physiologically relevant for stress tolerance. Salt stress induces an immediate metabolic readjustment, which includes the up-regulation of peroxisomal biomass and activity in a coordinated manner with the reinforcement of mitochondrial respiratory metabolism. Our recent findings are consistent with a model, where salt stress triggers a metabolic shift from fermentation to respiration fueled by the enhanced peroxisomal oxidation of fatty acids. 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Safety and toxicity evaluation of nutraceuticals in animal models.

Nutraceuticals are derived from various natural sources such as medicinal plants, marine organisms, vegetables, and fruits. Most of them possess antioxidant or anti-inflammatory properties and are claimed to provide protection against many diseases if taken regularly. At the same time, toxicological studies of nutraceuticals have been limited, so the safety of many of them cannot be guaranteed. Animals share many genetic, anatomical, and physiological similarities with humans, and they continue to be widely used in preclinical studies of drugs, in spite of a lack of their validity which is due to the great phenotypic differences. The absence of toxicity in animals provides little probability that adverse reactions will also be absent in humans. There are currently thousands of researchers involved in the development of alternatives to animal use in the life sciences. Statistical machine-learning tools, once developed, might become a powerful means to explain the complex physiological effects of nutraceuticals. The use of different models and algorithms can provide a more scientific basis for risk assessment of nutraceuticals for humans