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UCLA stem cell researchers uncover mechanism that regulates human pluripotent stem cell metabolism
Date:11/15/2011

Koehler, a UCLA professor of chemistry and biochemistry, for the study.

"A lot of attention is being paid to the role of metabolism in pluripotent stem cells for making properly differentiated cell lineages for research and potential clinical uses," said study senior author Dr. Michael Teitell, a researcher with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA and a professor of pediatrics, pathology and laboratory medicine, and bioengineering.

The initial question prompting our study was whether metabolism in pluripotent stem cells and cancer cells, which also rely heavily on glycolysis, were molecularly similar," he said. "This question led us to study the details of energy-generation by mitochondria in pluripotent stem cells."

Cells make energy in the form of ATP mainly in two ways, by glucose uptake and fermentation in the cytoplasm or by using respiration, in which glucose and oxygen are consumed to make carbon dioxide and water to fuel cell functions. Teitell and his team expected that pluripotent stem cells could not respire because of prior reports on the immature appearance and paucity of mitochondria.

Teitell's team found that the molecular complexes responsible for respiration, called the electron transport chain, in the mitochondria of pluripotent stem cells were functional, and yet the cells instead relied on glycolysis for energy production. The researchers speculated that there were one or more unknown regulators that kept the stem cells from respiring, since the electron transport chain was functional.

Jin Zhang, a graduate student and first author of the study, discovered that a protein called uncoupling protein 2 (UCP2), was highly expressed in the stem cells. He also found that UCP2 blocked respiration substrates derived from sugar from gaining access to the mitochondria, instead shunting them to the glycolytic and biosynthesis pathways located in the cytoplasm, i
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Contact: Kim Irwin
kirwin@mednet.ucla.edu
310-206-2805
University of California - Los Angeles Health Sciences
Source:Eurekalert

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