2015
DOI: 10.1016/j.cmet.2015.01.017
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Pyruvate Kinase M2 Regulates Hif-1α Activity and IL-1β Induction and Is a Critical Determinant of the Warburg Effect in LPS-Activated Macrophages

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Cited by 280 publications
(362 citation statements)
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“…However, it has been widely reported that hypoxia inducible factor 1α (HIF1α) can be stabilized after LPS sensing in macrophages and maintains glycolysis over the long‐term by enhancing glycolytic gene expression . HIF1α can work in concert with an isozyme of pyruvate kinase (PKM2) . Normally inactive, dimeric/monomeric PKM2 translocates to the nucleus and is involved in the activation of HIF1α target genes, reportedly via a kinase activity rather than its enzyme function, although this remains controversial .…”
Section: Functional Diversity In Phagocytic Cellsmentioning
confidence: 99%
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“…However, it has been widely reported that hypoxia inducible factor 1α (HIF1α) can be stabilized after LPS sensing in macrophages and maintains glycolysis over the long‐term by enhancing glycolytic gene expression . HIF1α can work in concert with an isozyme of pyruvate kinase (PKM2) . Normally inactive, dimeric/monomeric PKM2 translocates to the nucleus and is involved in the activation of HIF1α target genes, reportedly via a kinase activity rather than its enzyme function, although this remains controversial .…”
Section: Functional Diversity In Phagocytic Cellsmentioning
confidence: 99%
“…HIF1α can work in concert with an isozyme of pyruvate kinase (PKM2) . Normally inactive, dimeric/monomeric PKM2 translocates to the nucleus and is involved in the activation of HIF1α target genes, reportedly via a kinase activity rather than its enzyme function, although this remains controversial . PKM2 is not the only metabolic enzyme to exhibit moonlighting activity: aconitase is also known as iron regulatory protein 1 and can control the translation of mRNAs containing iron‐responsive elements and GAPDH can bind AU‐rich elements of mRNA, such as IFN‐γ.…”
Section: Functional Diversity In Phagocytic Cellsmentioning
confidence: 99%
“…Mitochondria are subcellular organelles that play vital roles in the eukaryotic cells. Even though their function in energy metabolism is extensively recognized, only a few years ago, several studies demonstrated the relevance of mitochondria in immunity as a platform for immune regulation (29,(44)(45)(46)(47)(48). Mitochondrial function could be assessed by respiration driving ATP production, respiration driving proton leak, maximal respiration, and spare respiratory capacity, among others.…”
Section: Discussionmentioning
confidence: 99%
“…Treatment of macrophages with LPS results in significant succinate accumulation along with an increased expression of HIF‐1α protein . During inflammatory activation of myeloid cells, increased HIF‐1α expression also drives increased expression of IL‐1β and promotes inflammation . Thus, succinate stabilizes HIF‐1α even under normoxic conditions in myeloid and acts as an important inflammatory signal (Fig.…”
Section: Succinatementioning
confidence: 98%
“…Pharmacologic activation of PKM2 in SIRT5 knockout (KO) macrophages lead to inhibition of LPS‐induced IL‐1β, with no effect on IL‐6 and TNF‐α . LPS‐induced succinylation of PKM2 promotes its translocation to the nucleus, where it formed a complex that directly bound the IL‐1β promoter and induced its transcription . Furthermore, Tannahill et al.…”
Section: Succinatementioning
confidence: 99%