Format

Send to

Choose Destination
See comment in PubMed Commons below
Cancer Res. 2009 Mar 15;69(6):2163-6. doi: 10.1158/0008-5472.CAN-08-3722. Epub 2009 Mar 3.

Mitochondrial uncoupling and the Warburg effect: molecular basis for the reprogramming of cancer cell metabolism.

Author information

1
Section of Molecular Hematology and Therapy, Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.

Abstract

The precise mitochondrial alterations that underlie the increased dependence of cancer cells on aerobic glycolysis for energy generation have remained a mystery. Recent evidence suggests that mitochondrial uncoupling-the abrogation of ATP synthesis in response to mitochondrial membrane potential-promotes the Warburg effect in leukemia cells, and may contribute to chemoresistance. Intriguingly, leukemia cells cultured on bone marrow-derived stromal feeder layers are more resistant to chemotherapy, increase the expression of uncoupling protein 2, and decrease the entry of pyruvate into the Krebs cycle-without compromising the consumption of oxygen, suggesting a shift to the oxidation of nonglucose carbon sources to maintain mitochondrial integrity and function. Because fatty acid oxidation has been linked to chemoresistance and mitochondrial uncoupling, it is tempting to speculate that Warburg's observations may indeed be the result of the preferential oxidation of fatty acids by cancer cell mitochondria. Therefore, targeting fatty acid oxidation or anaplerotic pathways that support fatty acid oxidation may provide additional therapeutic tools for the treatment of hematopoietic malignancies.

PMID:
19258498
PMCID:
PMC3822436
DOI:
10.1158/0008-5472.CAN-08-3722
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center