Format

Send to:

Choose Destination
See comment in PubMed Commons below
Nat Cell Biol. 2008 Dec;10(12):1477-83. doi: 10.1038/ncb1807. Epub 2008 Nov 23.

Glucose metabolism inhibits apoptosis in neurons and cancer cells by redox inactivation of cytochrome c.

Author information

  • 1Department of Cell & Developmental Biology, Box 7250, 115 Mason Farm Road, Chapel Hill, North Carolina 27599, USA.

Abstract

Neurons and cancer cells use glucose extensively, yet the precise advantage of this adaptation remains unclear. These two seemingly disparate cell types also show an increased regulation of the apoptotic pathway, which allows for their long-term survival. Here we show that both neurons and cancer cells strictly inhibit cytochrome c-mediated apoptosis by a mechanism dependent on glucose metabolism. We report that the pro-apoptotic activity of cytochrome c is influenced by its redox state and that increases in reactive oxygen species (ROS) following an apoptotic insult lead to the oxidation and activation of cytochrome c. In healthy neurons and cancer cells, however, cytochrome c is reduced and held inactive by intracellular glutathione (GSH), generated as a result of glucose metabolism by the pentose phosphate pathway. These results uncover a striking similarity in apoptosis regulation between neurons and cancer cells and provide insight into an adaptive advantage offered by the Warburg effect for cancer cell evasion of apoptosis and for long-term neuronal survival.

PMID:
19029908
[PubMed - indexed for MEDLINE]
PMCID:
PMC2626347
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Write to the Help Desk