TY - JOUR
T1 - Glucose feeds the tricarboxylic acid cycle via excreted ethanol in fermenting yeast
AU - Xiao, Tianxia
AU - Khan, Artem
AU - Shen, Yihui
AU - Chen, Li
AU - Rabinowitz, Joshua D.
N1 - Funding Information:
We thank S. Silverman and D. Botstein for access to the yeast knockout collection; T. TeSlaa, R. Ryseck and A. J. Cowan for feedback on the manuscript; I. Pelczer and J. Eng for assistance with NMR and mass spectrometry; C.M. Call for help with preliminary experiments; and M. Seyedsayamdost and members of the Rabinowitz laboratory for helpful discussions. Services, results and/or products in support of the research project were generated by the Rutgers Cancer Institute of New Jersey Metabolomics Shared Resource, supported, in part, with funding from NCI-CCSG P30CA072720-5923. This work was funded by U.S. Department of Energy grant DE-SC0018260 and the Department of Energy Center for Advanced Bioenergy and Bioproducts Innovation (award no. DE-SC0018420). Any opinions, findings, conclusions or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the views of the U.S. Department of Energy.
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2022/12
Y1 - 2022/12
N2 - Ethanol and lactate are typical waste products of glucose fermentation. In mammals, glucose is catabolized by glycolysis into circulating lactate, which is broadly used throughout the body as a carbohydrate fuel. Individual cells can both uptake and excrete lactate, uncoupling glycolysis from glucose oxidation. Here we show that similar uncoupling occurs in budding yeast batch cultures of Saccharomyces cerevisiae and Issatchenkia orientalis. Even in fermenting S. cerevisiae that is net releasing ethanol, media 13C-ethanol rapidly enters and is oxidized to acetaldehyde and acetyl-CoA. This is evident in exogenous ethanol being a major source of both cytosolic and mitochondrial acetyl units. 2H-tracing reveals that ethanol is also a major source of both NADH and NADPH high-energy electrons, and this role is augmented under oxidative stress conditions. Thus, uncoupling of glycolysis from the oxidation of glucose-derived carbon via rapidly reversible reactions is a conserved feature of eukaryotic metabolism. [Figure not available: see fulltext.].
AB - Ethanol and lactate are typical waste products of glucose fermentation. In mammals, glucose is catabolized by glycolysis into circulating lactate, which is broadly used throughout the body as a carbohydrate fuel. Individual cells can both uptake and excrete lactate, uncoupling glycolysis from glucose oxidation. Here we show that similar uncoupling occurs in budding yeast batch cultures of Saccharomyces cerevisiae and Issatchenkia orientalis. Even in fermenting S. cerevisiae that is net releasing ethanol, media 13C-ethanol rapidly enters and is oxidized to acetaldehyde and acetyl-CoA. This is evident in exogenous ethanol being a major source of both cytosolic and mitochondrial acetyl units. 2H-tracing reveals that ethanol is also a major source of both NADH and NADPH high-energy electrons, and this role is augmented under oxidative stress conditions. Thus, uncoupling of glycolysis from the oxidation of glucose-derived carbon via rapidly reversible reactions is a conserved feature of eukaryotic metabolism. [Figure not available: see fulltext.].
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U2 - 10.1038/s41589-022-01091-7
DO - 10.1038/s41589-022-01091-7
M3 - Article
C2 - 35970997
AN - SCOPUS:85135960432
SN - 1552-4450
VL - 18
SP - 1380
EP - 1387
JO - Nature Chemical Biology
JF - Nature Chemical Biology
IS - 12
ER -