Bhat A~Sengupta S, 2019

Pubmed ID 31416893
Title Ncl1-mediated metabolic rewiring critical during metabolic stress.
Authors Ajay Bhat, Rahul Chakraborty, Khushboo Adlakha, Ganesh Agam, Kausik Chakraborty, Shantanu Sengupta
Abstract 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.
Citation Life Sci Alliance 2019; 2:.

Datasets

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Paper Phenotype Condition Medium Collection Tested mutants Data Details
Bhat A~Sengupta S, 2019 growth (culture turbidity) L-cysteine [1 mM] SC (2) hap a 4,397 Quantitative

Curation history

Data

July 23, 2020 Clarification needed.
July 28, 2020 Request sent.
Aug. 7, 2020 Ready to load.
Aug. 12, 2020 Loaded.

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July 23, 2020 To request.
July 28, 2020 Request sent.
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Aug. 12, 2020 Loaded.