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Four Key Steps Control Glycolytic Flux in Mammalian Cells.

Author(s): Tanner, Lukas Bahati; Goglia, Alexander G; Wei, Monica H; Sehgal, Talen; Parsons, Lance R; et al

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Abstract: Altered glycolysis is a hallmark of diseases including diabetes and cancer. Despite intensive study of the contributions of individual glycolytic enzymes, systems-level analyses of flux control through glycolysis remain limited. Here, we overexpress in two mammalian cell lines the individual enzymes catalyzing each of the 12 steps linking extracellular glucose to excreted lactate, and find substantial flux control at four steps: glucose import, hexokinase, phosphofructokinase, and lactate export (and not at any steps of lower glycolysis). The four fluxcontrolling steps are specifically up-regulated by the Ras oncogene: optogenetic Ras activation rapidly induces the transcription of isozymes catalyzing these four steps and enhances glycolysis. At least one isozyme catalyzing each of these four steps is consistently elevated in human tumors. Thus, in the studied contexts, flux control in glycolysis is concentrated in four key enzymatic steps. Up-regulation of these steps in tumors likely underlies the Warburg effect.
Publication Date: 27-Jun-2018
Electronic Publication Date: 27-Jun-2018
Citation: Tanner, Lukas Bahati, Goglia, Alexander G, Wei, Monica H, Sehgal, Talen, Parsons, Lance R, Park, Junyoung O, White, Eileen, Toettcher, Jared E, Rabinowitz, Joshua D. (2018). Four Key Steps Control Glycolytic Flux in Mammalian Cells.. Cell systems, 7 (1), 49 - 62.e8. doi:10.1016/j.cels.2018.06.003
DOI: doi:10.1016/j.cels.2018.06.003
ISSN: 2405-4712
EISSN: 2405-4720
Pages: 49 - 62
Language: eng
Type of Material: Journal Article
Journal/Proceeding Title: Cell Systems
Version: Author's manuscript

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