These auxotrophs have made it convenient to study this organism as described later in the text and made significant contributions to research in various fields (Seike et al. pombe, Leu auxotrophs have been used since the latter half of the twentieth century (Kohli et al. This chronological lifespan extension by Leu starvation occurs in Leu auxotrophic cells but not in prototrophic cells (Ohtsuka et al. Starvation of Leu, one of the BCAAs, has also been found to activate the general amino acid control and extend the chronological lifespan in S. cerevisiae, restriction of methionine, asparagine, or glutamate (Glu) has been reported to extend the chronological lifespan, which is defined as the survival of a cell population after the stationary phase (Powers et al. In yeasts such as the budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe, cells can synthesize all amino acids, but a defect in the amino acid biosynthetic pathway leads to the loss of synthetic ability, resulting in activation of the general amino acid control and suppression of the TOR pathway, depending on the growth environment (Zaborske et al. Restrictions on methionine and tryptophan have been shown to reduce the activity of nutrient-sensing pathways and extend the lifespan in mice (Fontana and Partridge 2015). 2020), and an accurate understanding of this phenomenon will contribute to a wide range of life science fields, including antiaging.Īmino acid or protein restriction causes activation of general amino acid control and suppression of the target of rapamycin (TOR) pathway, leading to improved metabolic fitness, increased stress tolerance, and extended lifespan (Gallinetti et al. Various studies have reported a relationship between the lifespan of organisms and the presence of essential amino acids including Leu (Fontana and Partridge 2015, Ohtsuka et al. Since BCAA biosynthetic pathways exist in plant, fungi, archaea, and bacteria, but not in animals, these pathways may also be targets for herbicides and antimicrobial compounds (Liu et al. As the most bioactive BCAA, Leu contributes to the maintenance of the level of cellular acetyl coenzyme A and the acetylation of cytoplasmic proteins during nutrient deprivation (Mariño et al. It has important physiological functions in protein synthesis, metabolism, nutrient uptake, and control of aging (Le Couteur et al. It is also one of the essential amino acids in animals, including nematodes, silkworms, and humans (Oda 2007, Le Couteur et al. Leucine (Leu) is one of the branched-chain amino acids (BCAAs) like isoleucine (Ile) and valine (Val). An accurate understanding of the intracellular responses brought about by Leu auxotrophy can contribute to research in various fields using this model organism and to the understanding of intracellular responses in higher organisms that cannot synthesize Leu.įission yeast, Schizosaccharomyces pombe, leucine, leu1-32, general amino acid control, TORC1 Introduction pombe and discusses biosynthetic pathways, contribution to experimental convenience using a plasmid specific for Leu auxotrophic yeast, signaling pathways, and phenotypes caused by Leu starvation. This mini-review focuses on the roles of Leu in S. Under amino acid starvation, the amino acid-auxotrophic yeast induces cellular responses, which are conserved in higher organisms without the ability of synthesizing amino acids. Leu auxotrophy produces intracellular responses and phenotypes different from those of the prototrophic strains, depending on the growing environment, which necessitates a certain degree of caution in the analysis and interpretation of the experimental results. In this yeast, although a mutation in the Leu biosynthetic pathway, leu1-32, is clearly inconvenient for this species, it has increased its usefulness as a model organism in laboratories worldwide. Fungi, including the fission yeast Schizosaccharomyces pombe, can biosynthesize Leu, but deletion of any of the genes in this biosynthesis leads to Leu auxotrophy. Leucine (Leu) is a branched-chain, essential amino acid in animals, including humans.
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