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© The Rockefeller University Press, 0021-9525/2003/2/961 $5.00
The Journal of Cell Biology, Volume 162, Number 6, 961-961

Survival is sweet

BAD is needed for a proper response to glucose. Korsmeyer/Macmillan

Nutrition and cell death are integrated in a single mitochondrial complex, according to Nika Danial, Stanley Korsmeyer (Harvard Medical School, Boston, MA), and colleagues.

The complex was discovered after gel filtration of the pro-apoptotic BAD protein, and contains BAD, a phosphatase, kinase, and kinase-anchoring protein directed at BAD, and glucokinase. In cells lacking BAD, the complex falls apart, respiration is compromised, and blood glucose regulation is abnormal. A nonphosphorylatable BAD leaves the complex intact but otherwise nonresponsive to glucose.

The results are consistent with a simple model: glucose induces phosphorylation of BAD, thus ensuring both cell survival and activation of glucokinase. The active glucokinase clears blood glucose and feeds the mitochondrion with necessary intermediates.

The presumption was always that the cell's two major survival pathways— glycolysis and apoptosis—were independent. But the complex hints at integration. Korsmeyer speculates that early cells may have relied on this direct integration with sugar levels, as the cells probably lacked fancy growth factors for modulating cell survival. "We could be looking at a primordial role between nutrition and cell death," he says. "The growth factors may have come later." This hypothesis is consistent with the ideas of Craig Thompson (University of Pennsylvania, Philadelphia, PA), who has suggested that growth factors act not directly on cell survival but via modulation of glucose levels.

Reference:

Danial, N.N., et al. 2003. Nature. 424:952–956.[CrossRef][Medline]

William A. Wells

wellsw{at}rockefeller.edu

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This Article Full Text (PDF, 603K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wells, W. A. Search for Related Content PubMed Articles by Wells, W. A. Social Bookmarking                            What's this?