Pyruvate kinase isoenzyme M2 is a glycolytic sensor differentially regulating cell proliferation, cell size and apoptotic cell death dependent on glucose supply.
The glycolytic key regulator pyruvate kinase M2 (M2-PK or PKM2) can switch between a highly active tetrameric and an inactive dimeric form. The transition between the two conformations regulates the glycolytic flux in tumor cells. We developed specific M2-PK-binding peptide aptamers which inhibit M2-PK, but not the 96% homologous M1-PK isoenzyme. In this study we demonstrate that, at normal blood glucose concentrations, peptide aptamer-mediated inhibition of M2-PK induces a significant decrease of the population doubling (PDL rate) and cell proliferation rate as well as an increase in cell size, whereas under glucose restriction an increase in PDL and cell proliferation rates but a decrease in cell size was observed. Moreover, M2-PK inhibition rescues cells from glucose starvation-induced apoptotic cell death by increasing the metabolic activity. These findings suggest that M2-PK is a metabolic sensor which regulates cell proliferation, cell growth and apoptotic cell death in a glucose supply-dependent manner.
Spoden
Gilles A
GA
Department of Cell Metabolism and Differentiation, Institute for Biomedical Aging Research of the Austrian Academy of Sciences, Rennweg 10, 6020 Innsbruck, Austria.
Rostek
Ursula
U
Lechner
Stefan
S
Mitterberger
Maria
M
Mazurek
Sybille
S
Zwerschke
Werner
W
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D052158:Aptamers, Peptide / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D048429:Cell Size; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D011770:Pyruvate Kinase / Q000235:genetics / Q000378:metabolism*
D052158:Aptamers, Peptide; D007527:Isoenzymes; D011770:Pyruvate Kinase; D005947:Glucose