Glutathione efflux and cell death.
CONCLUSIONS
Glutathione (GSH) depletion is a central signaling event that regulates the activation of cell death pathways. GSH depletion is often taken as a marker of oxidative stress and thus, as a consequence of its antioxidant properties scavenging reactive species of both oxygen and nitrogen (ROS/RNS).


BACKGROUND
There is increasing evidence demonstrating that GSH loss is an active phenomenon regulating the redox signaling events modulating cell death activation and progression.


RESULTS
In this work, we review the role of GSH depletion by its efflux, as an important event regulating alterations in the cellular redox balance during cell death independent from oxidative stress and ROS/RNS formation. We discuss the mechanisms involved in GSH efflux during cell death progression and the redox signaling events by which GSH depletion regulates the activation of the cell death machinery.


CONCLUSIONS
The evidence summarized here clearly places GSH transport as a central mechanism mediating redox signaling during cell death progression. Future studies should be directed toward identifying the molecular identity of GSH transporters mediating GSH extrusion during cell death, and addressing the lack of sensitive approaches to quantify GSH efflux.
Redox Biology Center, University of Nebraska-Lincoln, Lincoln, NE 68583, USA. rfrancocruz2@unl.edu
Rodrigo
R
Franco
John A
JA
Cidlowski
D000818:Animals; D001692:Biological Transport; D016923:Cell Death / Q000502:physiology*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D015398:Signal Transduction
D005978:Glutathione