Science at the Edge
Interdisciplinary Physics
Friday October 26, 2012
11:30 BPS 1400
Mitochondrial Oxidant Stress/signaling:
Detection, Modification and Consequences in Health and Disease
Paul Schumacker
Northwestern University
Depts. of Pediatrics, Medicine and Cell & Molecular Biology
Abstract
Excessive oxidant stress induces damage to lipids, proteins and DNA, but low levels of reactive oxygen species (ROS) can function as signaling messengers in cells. In that regard, superoxide anion acts principally by interacting with iron-sulfur centers in proteins, while hydrogen peroxide (H2O2) acts primarily by altering protein thiol status. The generation of inter- or intra-molecular dithiols can influence protein function by causing important changes in protein structure. These changes are reversible by thiol oxido-reductases such as thioredoxin or glutaredoxin.
Our work implicates mitochondria as an important source of ROS signals in response to cellular stress. For example, hypoxia induces ROS release from the mitochondrial inner membrane to the intermembrane space, where it can act on specific targets. H2O2 in the intermembrane space can also diffuse to the cytosol, where it can trigger functional responses including transcription factor activation, calcium signaling, and AMPK activation. Understanding of where and how ROs signals act in the cell requires an ability to assess their effects in subcellular compartments. To address this we have expressed thiol redox-sensitive fluorescent protein sensors in subcellular compartments, allowing us to assess redox signaling in real time in response to cellular stresses. These studies are broadly of interest to a wide range of pathophysiological processes including cardiovascular, neurodegenerative, and pulmonary diseases.
http://www.feinberg.northwestern.edu/lab/Schumacker/
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To meet with the speaker on Oct 25 or 26th please contact R. Ghosh ([log in to unmask])
Shawna Prater / Secretary
Astrophysics Group
Michigan State University
567 Wilson Road, Room 3261
Biomedical Physical Sciences Bldg
East Lansing, MI 48824-2320
Ph: (517) 884-5601 Fax (517) 432-8802
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