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The Lifespan-regulator p66Shc in mitochondria: redox enzyme or redox sensor?
MedLine Citation:
PMID:  20214499     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Mitochondria contribute to various diseases and aging phenotypes. Reactive oxygen species (ROS), mainly formed by the respiratory chain, were long thought to cause these effects by damaging proteins, DNA, and lipids. The emerging understanding that ROS act not only destructively but also as dedicated signaling molecules, and that aging processes are regulated by specific signaling networks has stimulated research on mitochondrial signaling systems and the regulation of mitochondrial ROS metabolism. p66Shc is a lifespan-regulating protein contributing to mitochondrial ROS metabolism and regulating the mitochondrial apoptosis pathway. It was found to participate in aging processes and has been implicated in several pathologies. Considerable progress has been made recently concerning the molecular function of p66Shc. It appears that p66Shc responds to a variety of proapoptotic stimuli by increasing ROS levels in the mitochondrial intermembrane space through an inherent ROS-producing activity, and that this ROS formation might trigger initiation of the mitochondrial apoptosis pathway. In this review, we will discuss the current knowledge on the molecular architecture of the p66Shc protein, its role in ROS metabolism and apoptosis regulation in the mitochondrial intermembrane space, the regulation of its mitochondrial transport, and the molecular mechanisms and interactions involved in these processes.
Authors:
Melanie Gertz; Clemens Steegborn
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Antioxidants & redox signaling     Volume:  13     ISSN:  1557-7716     ISO Abbreviation:  Antioxid. Redox Signal.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-09-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100888899     Medline TA:  Antioxid Redox Signal     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1417-28     Citation Subset:  IM    
Affiliation:
Department of Physiological Chemistry, Ruhr-University Bochum, Germany.
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