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Ncl1-mediated metabolic rewiring critical during metabolic stress
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Ncl1-mediated metabolic rewiring critical during metabolic stress
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Journal Article
Ncl1-mediated metabolic rewiring critical during metabolic stress
2019
Overview
Nutritional limitation has been vastly studied; however, there is limited knowledge of how cells maintain homeostasis in excess nutrients. In this study, using yeast as a model system, we show that some amino acids are toxic at higher concentrations. With cysteine as a physiologically relevant example, we delineated the pathways/processes that are altered and those that are involved in survival in the presence of elevated levels of this amino acid. Using proteomics and metabolomics approach, we found that cysteine up-regulates proteins involved in amino acid metabolism, alters amino acid levels, and inhibits protein translation—events that are rescued by leucine supplementation. Through a comprehensive genetic screen, we show that leucine-mediated effect depends on a transfer RNA methyltransferase (NCL1), absence of which decouples transcription and translation in the cell, inhibits the conversion of leucine to ketoisocaproate, and leads to tricarboxylic acid cycle block. We therefore propose a role of NCL1 in regulating metabolic homeostasis through translational control.
Publisher
Life Science Alliance,Life Science Alliance LLC
Subject
/ Cysteine
/ Gene Expression Regulation, Fungal - drug effects
/ Leucine
/ Microbial Viability - drug effects
/ Proteins
/ Saccharomyces cerevisiae - drug effects
/ Saccharomyces cerevisiae - growth & development
/ Saccharomyces cerevisiae - metabolism
/ Saccharomyces cerevisiae Proteins - metabolism
/ Toxicity
/ tRNA Methyltransferases - metabolism
/ Yeast
