@article{d33d402ba70e48dd8c26ed32e6b1cc68,
title = "Evolved resistance to partial GAPDH inhibition results in loss of the Warburg effect and in a different state of glycolysis",
abstract = "Aerobic glycolysis or the Warburg effect (WE) is characterized by increased glucose uptake and incomplete oxidation to lactate. Although the WE is ubiquitous, its biological role remains controversial, and whether glucose metabolism is functionally different during fully oxidative glycolysis or during the WE is unknown. To investigate this question, here we evolved resistance to koningic acid (KA), a natural product that specifically inhibits glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a rate-controlling glycolytic enzyme, during the WE. We found that KA-resistant cells lose theWEbut continue to conduct glycolysis and surprisingly remain dependent on glucose as a carbon source and also on central carbon metabolism. Consequently, this altered state of glycolysis led to differential metabolic activity and requirements, including emergent activities in and dependences on fatty acid metabolism. These findings reveal that aerobic glycolysis is a process functionally distinct from conventional glucose metabolism and leads to distinct metabolic requirements and biological functions.",
author = "Liberti, {Maria V.} and Allen, {Annamarie E.} and Vijyendra Ramesh and Ziwei Dai and Singleton, {Katherine R.} and Zufeng Guo and Liu, {Jun O.} and Wood, {Kris C.} and Locasale, {Jason W.}",
note = "Funding Information: This work was supported by National Institutes of Health Grants R01CA193256 (to J. W. L.), R00CA168997 (to J. W. L.), and F99CA222986 (to M. V. L.); National Science Foundation Grant DGE-1144153 (to M. V. L.); and the Sloan Foundation (to M. V. L.). Z. G. and J. O. L. are inventors on a Johns Hopkins University patent covering E11 and its use as a glucose transport-er-1 inhibitor. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: This work was supported by National Institutes of Health Grants R01CA193256 (to J. W. L.), R00CA168997 (to J. W. L.), and F99CA222986 (to M. V. L.); National Science Foundation Grant DGE-1144153 (to M. V. L.); and the Sloan Foundation (to M. V. L.). Z. G. and J. O. L. are inventors on a Johns Hopkins University patent covering E11 and its use as a glucose transporter- 1 inhibitor. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2020 Liberti et al.",
year = "2020",
month = jan,
day = "3",
doi = "10.1074/jbc.RA119.010903",
language = "English (US)",
volume = "295",
pages = "111--124",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "1",
}