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


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:
Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
Additional Information: © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
Uncontrolled Keywords: bioenergetics,glycolysis,hypoxia,metabolism,sumoylation
Publication ISSN: 1083-351X
Last Modified: 27 Jun 2024 08:15
Date Deposited: 01 Oct 2013 10:03
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Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
http://www.jbc. ... tent/286/6/4718 (Publisher URL)
PURE Output Type: Article
Published Date: 2011-02-11
Published Online Date: 2010-12-01
Authors: Agbor, Terence A.
Cheong, Alex (ORCID Profile 0000-0003-2482-9078)
Comerford, Katrina M.
Scholz, Carsten C.
Bruning, Ulrike
Clarke, Ambrose
Cummins, Eoin P.
Cagney, Gerard
Taylor, Cormac T.



Version: Published Version

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