Bcl-xL complements Saccharomyces cerevisiae genes that facilitate the switch from glycolytic to oxidative metabolism

Matthew G. Vander Heiden, John S. Choy, David J. VanderWeele, Jennifer L. Brace, Marian H. Harris, Daniel E. Bauer, Bryan Prange, Stephen J. Kronll, Craig B. Thompson, Charles M. Rudin

Research output: Contribution to journalArticle

Abstract

All eukaryotic organisms have mechanisms to adapt to changing metabolic conditions. The mammalian cell survival gene Bcl-xL enables cells to adapt to changes in cellular metabolism. To identify genes whose function can be substituted by Bcl-xL in a unicellular eukaryote, a genetic screen was performed using the yeast Saccharomyces cerevisiae. S. cerevisiae grows by anaerobic glycolysis when glucose is available, switching to oxidative phosphorylation when carbohydrate in the media becomes limiting (diauxic shift). Given that Bcl-xL, appears to facilitate the switch from glycolytic to oxidative metabolism in mammalian cells, a library of yeast mutants was tested for the ability to efficiently undergo diauxic shift in the presence and absence of Bcl-xL. Several mutants were identified that have a defect in growth when switched from a fermentable to a nonfermentable carbon source that is corrected by the expression of Bcl-xL. These genes include the mitochondrial chaperonin TCM62, as well as previously uncharacterized genes. One of these uncharacterized genes, SVF1, promotes cell survival in mammalian cells in response to multiple apoptotic stimuli. The finding that TCM62 and the analogous human prohibitin gene also inhibit mammalian cell death following growth factor withdrawal implicates mitochondrial chaperones as regulators of apoptosis. Further characterization of the genes identified in this screen may enhance our understanding of Bcl-xL, function in mammalian cells, and of cell survival pathways in general.

Original languageEnglish (US)
Pages (from-to)44870-44876
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number47
DOIs
StatePublished - Nov 22 2002
Externally publishedYes

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Switch Genes
Metabolism
Yeast
Saccharomyces cerevisiae
Genes
Switches
Cells
Cell Survival
Yeasts
Chaperonins
Mitochondrial Genes
Oxidative Phosphorylation
Glycolysis
Eukaryota
Cell death
Libraries
Intercellular Signaling Peptides and Proteins
Cell Death
Carbon
Carbohydrates

ASJC Scopus subject areas

  • Biochemistry

Cite this

Vander Heiden, M. G., Choy, J. S., VanderWeele, D. J., Brace, J. L., Harris, M. H., Bauer, D. E., ... Rudin, C. M. (2002). Bcl-xL complements Saccharomyces cerevisiae genes that facilitate the switch from glycolytic to oxidative metabolism. Journal of Biological Chemistry, 277(47), 44870-44876. https://doi.org/10.1074/jbc.M204888200

Bcl-xL complements Saccharomyces cerevisiae genes that facilitate the switch from glycolytic to oxidative metabolism. / Vander Heiden, Matthew G.; Choy, John S.; VanderWeele, David J.; Brace, Jennifer L.; Harris, Marian H.; Bauer, Daniel E.; Prange, Bryan; Kronll, Stephen J.; Thompson, Craig B.; Rudin, Charles M.

In: Journal of Biological Chemistry, Vol. 277, No. 47, 22.11.2002, p. 44870-44876.

Research output: Contribution to journalArticle

Vander Heiden, MG, Choy, JS, VanderWeele, DJ, Brace, JL, Harris, MH, Bauer, DE, Prange, B, Kronll, SJ, Thompson, CB & Rudin, CM 2002, 'Bcl-xL complements Saccharomyces cerevisiae genes that facilitate the switch from glycolytic to oxidative metabolism', Journal of Biological Chemistry, vol. 277, no. 47, pp. 44870-44876. https://doi.org/10.1074/jbc.M204888200
Vander Heiden, Matthew G. ; Choy, John S. ; VanderWeele, David J. ; Brace, Jennifer L. ; Harris, Marian H. ; Bauer, Daniel E. ; Prange, Bryan ; Kronll, Stephen J. ; Thompson, Craig B. ; Rudin, Charles M. / Bcl-xL complements Saccharomyces cerevisiae genes that facilitate the switch from glycolytic to oxidative metabolism. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 47. pp. 44870-44876.
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