Nuclear and mitochondrial compartmentation of oxidative stress and redox signaling.
New methods to measure thiol oxidation show that redox compartmentation functions as a mechanism for specificity in redox signaling and oxidative stress. Redox Western analysis and redox-sensitive green fluorescent proteins provide means to quantify thiol/disulfide redox changes in specific subcellular compartments. Analyses using these techniques show that the relative redox states from most reducing to most oxidizing are mitochondria > nuclei > cytoplasm > endoplasmic reticulum > extracellular space. Mitochondrial thiols are an important target of oxidant-induced apoptosis and necrosis and are especially vulnerable to oxidation because of the relatively alkaline pH. Maintenance of a relatively reduced nuclear redox state is critical for transcription factor binding in transcriptional activation in response to oxidative stress. The new methods are applicable to a broad range of experimental systems and their use will provide improved understanding of the pharmacologic and toxicologic actions of drugs and toxicants.
Hansen
Jason M
JM
Department of Medicine and Clinical Biomarkers Laboratory, Division of Pulmonary Medicine, Emory University, Atlanta, GA 30322, USA. jhansen@emory.edu
Go
Young-Mi
YM
Jones
Dean P
DP
D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*