Small Ubiquitin-related Modifier (SUMO)-1 promotes glycolysis in hypoxia

Agbor, Terence A., Cheong, Alex, Comerford, Katrina M., Scholz, Carsten C., Bruning, Ulrike, Clarke, Ambrose, Cummins, Eoin P., Cagney, Gerard and Taylor, Cormac T. (2011). Small Ubiquitin-related Modifier (SUMO)-1 promotes glycolysis in hypoxia. Journal of Biological Chemistry, 286 (6), pp. 4718-4726.

Abstract

Under conditions of hypoxia, most eukaryotic cells undergo a shift in metabolic strategy, which involves increased flux through the glycolytic pathway. Although this is critical for bioenergetic homeostasis, the underlying mechanisms have remained incompletely understood. Here, we report that the induction of hypoxia-induced glycolysis is retained in cells when gene transcription or protein synthesis are inhibited suggesting the involvement of additional post-translational mechanisms. Post-translational protein modification by the small ubiquitin related modifier-1 (SUMO-1) is induced in hypoxia and mass spectrometric analysis using yeast cells expressing tap-tagged Smt3 (the yeast homolog of mammalian SUMO) revealed hypoxia-dependent modification of a number of key glycolytic enzymes. Overexpression of SUMO-1 in mammalian cancer cells resulted in increased hypoxia-induced glycolysis and resistance to hypoxia-dependent ATP depletion. Supporting this, non-transformed cells also demonstrated increased glucose uptake upon SUMO-1 overexpression. Conversely, cells overexpressing the de-SUMOylating enzyme SENP-2 failed to demonstrate hypoxia-induced glycolysis. SUMO-1 overexpressing cells demonstrated focal clustering of glycolytic enzymes in response to hypoxia leading us to hypothesize a role for SUMOylation in promoting spatial re-organization of the glycolytic pathway. In summary, we hypothesize that SUMO modification of key metabolic enzymes plays an important role in shifting cellular metabolic strategies toward increased flux through the glycolytic pathway during periods of hypoxic stress.

Publication DOI: https://doi.org/10.1074/jbc.M110.115931
Divisions: Life & Health Sciences > Pharmacy
Life & Health Sciences > Cellular and Molecular Biomedicine
Additional Information: © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
Uncontrolled Keywords: bioenergetics,glycolysis,hypoxia,metabolism,sumoylation
Full Text Link:
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
http://www.jbc. ... tent/286/6/4718 (Publisher URL)
Published Date: 2011-02-11
Authors: Agbor, Terence A.
Cheong, Alex ( 0000-0003-2482-9078)
Comerford, Katrina M.
Scholz, Carsten C.
Bruning, Ulrike
Clarke, Ambrose
Cummins, Eoin P.
Cagney, Gerard
Taylor, Cormac T.

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