Identification of thioredoxin-2 as a regulator of the mitochondrial permeability transition.
Thioredoxin-2 (Trx2) is a multifunctional, mitochondria-specific protein, which inhibits cell death. The mitochondrial permeability transition (MPT) is a distinct mechanism for cell death activated by oxidants and linked to both necrotic and apoptotic morphologies. We studied mitochondria from Trx2 transgenic mice to determine whether Trx2 protects against oxidant-induced MPT. All experiments were performed in isolated mitochondria. Results showed that Trx2 protected against MPT induced by exogenously added peroxide. Unexpectedly, Trx2 also protected against the MPT induced by Ca(2+) in the absence of added peroxide. The results indicate that in addition to protecting against oxidative stress, Trx2 is an endogenous regulator of the MPT.
He
Min
M
Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Emory University, Atlanta, GA 30322, USA.
Cai
Jiyang
J
Go
Young-Mi
YM
Johnson
Jennifer M
JM
Martin
W David
WD
Hansen
Jason M
JM
Jones
Dean P
DP
D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D005260:Female; D048848:MAP Kinase Kinase Kinase 5 / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D018384:Oxidative Stress; D013879:Thioredoxins / Q000502:physiology*
D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; C516112:Txn2 protein, mouse; D013879:Thioredoxins; D048848:MAP Kinase Kinase Kinase 5; C482859:Map3k5 protein, mouse; D002118:Calcium