dc.contributor.author |
MacDonald, J |
en |
dc.contributor.author |
Hickey, Anthony |
en |
dc.contributor.author |
Loomes, Kerry |
en |
dc.coverage.spatial |
Berlin |
en |
dc.date.accessioned |
2017-06-11T22:44:30Z |
en |
dc.date.issued |
2016 |
en |
dc.identifier.citation |
7th World Congress on Targeting Mitochondria, Berlin, 24 Oct 2016 - 26 Oct 2016. 2016 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/33409 |
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dc.description.abstract |
Background. Cancer cells divert their mitochondrial metabolism away from pyruvate derived from glycolysis and instead rely increasingly on glutamine as a fuel source (1). The mitochondrial enzyme, malic enzyme 2 (ME2), catalyses NADPH and pyruvate production from the Krebs cycle metabolite, malate. ME2 is upregulated in cancer and associated with cell invasion in melanoma (2,3). ME2 is of therapeutic interest as its knockdown attenuates cell proliferation, an effect mediated through decreased production of NADPH and anabolic capacity (3,4). We hypothesised that ME2 also enabled the cancer cell to adapt to glutamine as a fuel source by sustaining mitochondrial respiration through pyruvate produced through ME2. Objective. Using high resolution respirometry we investigated the ability of intact mitochondria isolated from HEK-293 cells to respire solely on malate. Under these conditions mitochondrial respiration might be expected to be significantly blunted. Results. Remarkably, respiration rates with malate were comparable to maximal rates observed in the presence of pyruvate and glutamate. Pharmacological inhibition of ME2 (5) abolished respiration rate by 67% showing ME2 was primarily responsible for maintaining respiration in the absence of exogenously-derived pyruvate. Conclusion. ME2 enables the cell to adapt to a diminished pyruvate fuel source by maintaining mitochondrial respiration. 1. Jin et al. (2015) Oncogene, 1-7 2. Chang et al. (2015) J Invest Dermatol 135, 807-815 3. Jiang et al. (2013) Nature 493, 689-693 4. Zheng, B., and Fisher, D. E. (2015) Journal of Investigative Dermatology 135, 657-659 5. Wen et al. (2014) Acta pharmacologica Sinica 35, 674-684 |
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dc.relation.ispartof |
7th World Congress on Targeting Mitochondria |
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dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
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dc.title |
Malic Enzyme-2 And Its Role In Maintaining Mitochondrial Respiration In HEK-293 Cells |
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dc.type |
Conference Item |
en |
pubs.author-url |
https://www.targeting-mitochondria.com/mitochondria-previous-conferences |
en |
pubs.finish-date |
2016-10-26 |
en |
pubs.start-date |
2016-10-24 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Proceedings |
en |
pubs.elements-id |
547231 |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
Biological Sciences |
en |
pubs.org-id |
Science Research |
en |
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
en |
pubs.record-created-at-source-date |
2016-11-28 |
en |
pubs.online-publication-date |
2016 |
en |