Glutaredoxin 2 Catalyzes the Reversible Oxidation and Glutathionylation of Mitochondrial Membrane Thiol Proteins: IMPLICATIONS FOR MITOCHONDRIAL REDOX REGULATION AND ANTIOXIDANT DEFENSE *

摘要: The redox poise of the mitochondrial glutathione pool is central in response mitochondria to oxidative damage and signaling, but mechanisms are uncertain. One possibility that oxidation (GSH) disulfide (GSSG) consequent change GSH/GSSG ratio causes protein thiols their state, enabling function respond reversibly signals damage. However, little known about interplay between thiols. Therefore we investigated how physiological ratios affected state membrane Exposure oxidized led reversible reactive by thiol-disulfide exchange, extent which was dependent on ratio. There an initial rapid phase thiol oxidation, followed gradual over 30 min. A large number proteins contain most these formed intraprotein disulfides upon GSSG; however, a small persistent mixed with glutathione. Both formation glutathionylation were catalyzed transferase glutaredoxin 2 (Grx2), as deglutathionylation reduction GSH. Complex I prominent persistently glutathionylated GSSG presence Grx2. Maintenance complex dramatic loss activity, suggesting may contribute selective inactivation seen Parkinson's disease. Most significantly, Grx2 glutathionylation/deglutathionylation wide range ratios, from reduced levels accessible under signaling only found severe stress. Our findings indicate plays role both stress facilitating