Journal article
The basic biology of redoxosomes in cytokine-mediated signal transduction and implications for disease-specific therapies
Biochemistry (Easton), Vol.53(10), pp.1551-1564
03/18/2014
DOI: 10.1021/bi401719r
PMCID: PMC3985689
PMID: 24555469
Abstract
Redox reactions have been established as major biological players in many cellular signaling pathways. Here we review mechanisms of redox signaling with an emphasis on redox-active signaling endosomes. Signals are transduced by relatively few reactive oxygen species (ROS), through very specific redox modifications of numerous proteins and enzymes. Although ROS signals are typically associated with cellular injury, these signaling pathways are also critical for maintaining cellular health at homeostasis. An important component of ROS signaling pertains to localization and tightly regulated signal transduction events within discrete microenvironments of the cell. One major aspect of this specificity is ROS compartmentalization within membrane-enclosed organelles such as redoxosomes (redox-active endosomes) and the nuclear envelope. Among the cellular proteins that produce superoxide are the NADPH oxidases (NOXes), transmembrane proteins that are implicated in many types of redox signaling. NOXes produce superoxide on only one side of a lipid bilayer; as such, their orientation dictates the compartmentalization of ROS and the local control of signaling events limited by ROS diffusion and/or movement through channels associated with the signaling membrane. NOX-dependent ROS signaling pathways can also be self-regulating, with molecular redox sensors that limit the local production of ROS required for effective signaling. ROS regulation of the Rac-GTPase, a required co-activator of many NOXes, is an example of this type of sensor. A deeper understanding of redox signaling pathways and the mechanisms that control their specificity will provide unique therapeutic opportunities for aging, cancer, ischemia-reperfusion injury, and neurodegenerative diseases.
Details
- Title: Subtitle
- The basic biology of redoxosomes in cytokine-mediated signal transduction and implications for disease-specific therapies
- Creators
- Netanya Y Spencer - Department of Anatomy and Cell Biology, The University of Iowa , Iowa City, Iowa 52242-1009, United StatesJohn F Engelhardt
- Resource Type
- Journal article
- Publication Details
- Biochemistry (Easton), Vol.53(10), pp.1551-1564
- Publisher
- United States
- DOI
- 10.1021/bi401719r
- PMID
- 24555469
- PMCID
- PMC3985689
- ISSN
- 0006-2960
- eISSN
- 1520-4995
- Grant note
- K01 DK083429 / NIDDK NIH HHS T32 HL007344 / NHLBI NIH HHS P30 DK054759 / NIDDK NIH HHS P30 DK54759 / NIDDK NIH HHS R01 DK051315 / NIDDK NIH HHS
- Language
- English
- Date published
- 03/18/2014
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984025453902771
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