PKM2 diverts glycolytic flux in dependence on mitochondrial one-carbon cycle [* Cross-Reference *]

Version 1.0
Mohaned Benzarti; Laura Neises; Anaïs Oudin; Christina Krötz; Elodie Viry; Ernesto Gargiulo; Coralie Pulido; Maryse Schmoetten; Vitaly I. Pozdeev; Nadia I. Lorenz; Michael Ronellenfitsch; David Sumpton; Marc O. Warmoes; Christian Jaeger; Antoine Lesur; Björn Becker; Etienne Moussay; Jérôme Paggetti; Simone P. Niclou; Elisabeth Letellier; Johannes Meiser, 2026, "PKM2 diverts glycolytic flux in dependence on mitochondrial one-carbon cycle [* Cross-Reference *]", https://lore.list.lu/citation?persistentId=perma:LIST.TXAZL1, LIST Open Repository, V1
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Description
Modeling tumor metabolism in vitro remains challenging. Here, we used galactose as an in vitro tool compound to mimic glycolytic limitation. In contrast to the established idea that high glycolytic flux reduces pyruvate kinase isozyme M2 (PKM2) activity to support anabolic processes, we have discovered that glycolytic limitation also affects PKM2 activity. Surprisingly, despite limited carbon availability and energetic stress, cells induce a near-complete block of PKM2 to divert carbons toward serine metabolism. Simultaneously, TCA cycle flux is sustained, and oxygen consumption is increased, supported by glutamine. Glutamine not only supports TCA cycle flux but also serine synthesis via distinct mechanisms that are directed through PKM2 inhibition. Finally, deleting mitochondrial one-carbon (1C) cycle reversed the PKM2 block, suggesting a potential formate-dependent crosstalk that coordinates mitochondrial 1C flux and cytosolic glycolysis to support cell survival and proliferation during nutrient-scarce conditions. (2024-02-28)
***This entry has been automatically imported via OpenAlex by LIST harvest scripts. Please refer to https://doi.org/10.1016/j.celrep.2024.113868 for the original and latest version of the publication*** (2026-07-01)
Subject Chemistry; Medicine, Health and Life Sciences
Keyword Flux (metallurgy), Glycolysis, Carbon flux, Citric acid cycle, PKM2, Carbon cycle, Chemistry, Cell biology, Physics, Biochemistry, Biology, Metabolism, Pyruvate kinase, Ecology
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