Electrophysiology of reactive oxygen production in signaling endosomes.
Journal Article (Journal Article;Review)
Endosome trafficking and function require acidification by the vacuolar ATPase (V-ATPase). Electrogenic proton (H+) transport reduces the pH and creates a net positive charge in the endosomal lumen. Concomitant chloride (Cl-) influx has been proposed to occur via ClC Cl-=H+ exchangers. This maintains charge balance and drives Cl- accumulation, which may itself be critical to endosome function. Production of reactive oxygen species (ROS) in response to cytokines occurs within specialized endosomes that form in response to receptor occupation. ROS production requires an NADPH oxidase (Nox) and the ClC-3 Cl-=H+ exchanger. Like the V-ATPase, Nox activity is highly electrogenic, but separates charge with an opposite polarity (lumen negative). Here we review established paradigms of early endosomal ion transport focusing on the relation between the V-ATPase and ClC proteins. Electrophysiologic constraints on Nox-mediated vesicular ROS production are then considered. The potential for ClC-3 to participate in charge neutralization of both proton (V-ATPase) and electron (Nox) transport is discussed. It is proposed that uncompensated charge separation generated by Nox enzymatic activity could be used to drive secondary transport into negatively charged vesicles. Further experimentation will be necessary to establish firmly the biochemistry and functional implications of endosomal ROS production.
Full Text
Duke Authors
Cited Authors
- Lamb, FS; Moreland, JG; Miller, FJ
Published Date
- June 2009
Published In
Volume / Issue
- 11 / 6
Start / End Page
- 1335 - 1347
PubMed ID
- 19207039
Pubmed Central ID
- PMC2872256
Electronic International Standard Serial Number (EISSN)
- 1557-7716
Digital Object Identifier (DOI)
- 10.1089/ars.2008.2448
Language
- eng
Conference Location
- United States