ArticlePLoS genetics2015
Branched-Chain Aminotransferases Control TORC1 Signaling in Saccharomyces cerevisiae.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 69 citations in OpenAlex.
- Distinctive domestication of farmhouse beer yeasts preserved pre-industrial genetic and phenotypic diversity.Current biology : CB · 2026Article
- An economic demand-based framework for prioritization strategies in response to transient amino acid limitations.Nature communications · 2024Article
- Transcriptome analysis reveals multiple targets of erythritol-related transcription factor EUF1 in unconventional yeast Yarrowia Lipolytica.Microbial cell factories · 2024Article
- Mycoparasitism related targets of Tmk1 indicate stimulating regulatory functions of this MAP kinase in Trichoderma atroviride.Scientific reports · 2023Article
- Branched-chain amino acid synthesis is coupled to TOR activation early in the cell cycle in yeast.EMBO reports · 2023Article
- Genetic effects on molecular network states explain complex traits.Molecular systems biology · 2023Article
- The Yeast Protein Kinase Sch9 Functions as a Central Nutrient-Responsive Hub That Calibrates Metabolic and Stress-Related Responses.Journal of fungi (Basel, Switzerland) · 2023Review
- Research progress on branched-chain amino acid aminotransferases.Frontiers in genetics · 2023Review
- Identification of a modulator of the actin cytoskeleton, mitochondria, nutrient metabolism and lifespan in yeast.Nature communications · 2022Article
- Cardiolipin function in the yeast S. cerevisiae and the lessons learned for Barth syndrome.Journal of inherited metabolic disease · 2022Review
- The mechanism of branched-chain amino acid transferases in different diseases: Research progress and future prospects.Frontiers in oncology · 2022Review
- An overview of branched-chain amino acid aminotransferases: functional differences between mitochondrial and cytosolic isozymes in yeast and human.Applied microbiology and biotechnology · 2021Review
- Kog1/Raptor mediates metabolic rewiring during nutrient limitation by controlling SNF1/AMPK activity.Science advances · 2021Article
- BCAT1 affects mitochondrial metabolism independently of leucine transamination in activated human macrophages.Journal of cell science · 2020Article
- Mitochondrial respiration is required to provide amino acids during fermentative proliferation of fission yeast.EMBO reports · 2020Article
- Metabolic excretion associated with nutrient-growth dysregulation promotes the rapid evolution of an overt metabolic defect.PLoS biology · 2020Article
- Increased Expression of UMAMIT Amino Acid Transporters Results in Activation of Salicylic Acid Dependent Stress Response.Frontiers in plant science · 2020Article
- The plasticity of the pyruvate dehydrogenase complex confers a labile structure that is associated with its catalytic activity.PloS one · 2020Article
- The cytosolic form of aspartate aminotransferase is required for full activation of TOR complex 1 in fission yeast.The Journal of biological chemistry · 2019Article
- Ncl1-mediated metabolic rewiring critical during metabolic stress.Life science alliance · 2019Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The conserved target of rapamycin complex 1 (TORC1) integrates nutrient signals to orchestrate cell growth and proliferation. Leucine availability is conveyed to control TORC1 activity via the leu-tRNA synthetase/EGOC-GTPase module in yeast and mammals, but the mechanisms sensing leucine remain only partially understood. We show here that both leucine and its α-ketoacid metabolite, α-ketoisocaproate, effectively activate the yeast TORC1 kinase via both EGOC GTPase-dependent and -independent mechanisms. Leucine and α-ketoisocaproate are interconverted by ubiquitous branched-chain aminotransferases (BCAT), which in yeast are represented by the mitochondrial and cytosolic enzymes Bat1 and Bat2, respectively. BCAT yeast mutants exhibit severely compromised TORC1 activity, which is partially restored by expression of Bat1 active site mutants, implicating both catalytic and structural roles of BCATs in TORC1 control. We find that Bat1 interacts with branched-chain amino acid metabolic enzymes and, in a leucine-dependent fashion, with the tricarboxylic acid (TCA)-cycle enzyme aconitase. BCAT mutation perturbed TCA-cycle intermediate levels, consistent with a TCA-cycle block, and resulted in low ATP levels, activation of AMPK, and TORC1 inhibition. We propose the biosynthetic capacity of BCAT and its role in forming multicomplex metabolons connecting branched-chain amino acids and TCA-cycle metabolism governs TCA-cycle flux to activate TORC1 signaling. Because mammalian mitochondrial BCAT is known to form a supramolecular branched-chain α-keto acid dehydrogenase enzyme complex that links leucine metabolism to the TCA-cycle, these findings establish a precedent for understanding TORC1 signaling in mammals.
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