Identification of Thioredoxin-2 as a Regulator of the Mitochondrial Permeability Transition

Min He; Jiyang Cai; Young-Mi Go; Jennifer M. Johnson; W. David Martin; Jason M. Hansen; Dean P. Jones
September 2008
Toxicological Sciences;Sep2008, Vol. 105 Issue 1, p44
Academic Journal
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 Ca2+ 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.


Related Articles

  • Mitochondria and ischemia�reperfusion injury of the heart: Fixing a hole. Di Lisa, Fabio; Bernardi, Paolo // Cardiovascular Research;May2006, Vol. 70 Issue 2, p191 

    Abstract: Ischemia and post-ischemic reperfusion cause a wide array of functional and structural alterations of mitochondria. Although mitochondrial impairment is recognized as pivotal in determining loss of viability, the causal relationships among the various processes involved is ill defined....

  • GAPDH binds to active Akt, leading to Bcl-xL increase and escape from caspase-independent cell death. Jacquin, M A; Chiche, J; Zunino, B; Bénéteau, M; Meynet, O; Pradelli, L A; Marchetti, S; Cornille, A; Carles, M; Ricci, J-E // Cell Death & Differentiation;Aug2013, Vol. 20 Issue 8, p1043 

    Increased glucose catabolism and resistance to cell death are hallmarks of cancers, but the link between them remains elusive. Remarkably, under conditions where caspases are inhibited, the process of cell death is delayed but rarely blocked, leading to the occurrence of caspase-independent cell...

  • Induction of Apoptosis-Like Mitochondrial Impairment Triggers Antioxidant and Bcl-2-Dependent Keratinocyte Differentiation. Tamiji, Susan; Beauvillain, Jean-Claude; Mortier, Laurent; Jouy, Nathalie; Tual, Martine; Delaporte, Emmanuel; Formstecher, Pierre; Marchetti, Philippe; Polakowska, Renata // Journal of Investigative Dermatology;Oct2005, Vol. 125 Issue 4, p647 

    Terminally differentiated keratinocytes are dead enucleated squams. We showed previously that the mitochondria-dependent cell death pathway might be gradually activated as differentiation progresses. In this study, we demonstrated that protoporphyrin IX, staurosporine, and rotenone induced...

  • Molecular ordering of hypoxia-induced apoptosis: critical involvement of the mitochondrial death pathway in a FADD/caspase-8 independent manner. Weinmann, Martin; Jendrossek, Verena; Handrick, Rene; Güner, Dilek; Goecke, Barbara; Belka, Claus // Oncogene;5/6/2004, Vol. 23 Issue 21, p3757 

    Dys-regulated growth and improper angiogenesis commonly lead to areas of hypoxia in human tumors. Hypoxia is known to be associated with a worse outcome since a tack of oxygen interferes with the efficacy of chemotherapy or radiotherapy. In parallel, hypoxia-induced apoptosis may also impose a...

  • Enforced dimerization of BAX results in its translocation, mitochondrial dysfunction and apoptosis. Gross, Atan; Jockel, Jennifer; Wei, Michael C.; Korsmeyer, Stanley J. // EMBO Journal;7/15/98, Vol. 17 Issue 14, p3878 

    Expression of the pro-apoptotic molecule BAX has been shown to induce cell death. While BAX forms both homo- and heterodimers, questions remain concerning its native conformation in vivo and which moiety is functionally active. Here we demonstrate that a physiologic death stimulus, the...

  • Intra-mitochondrial degradation of Tim23 curtails the survival of cells rescued from apoptosis by caspase inhibitors. Goemans, C. G.; Boya, P.; Skirrow, C. J.; Tolkovsky, A. M. // Cell Death & Differentiation;Mar2008, Vol. 15 Issue 3, p545 

    Caspase inhibition can extend the survival of cells undergoing apoptosis beyond the point of mitochondrial outer membrane permeabilisation (MOMP), but this does not confer long-term protection because caspase-independent death pathways emerge. Here, we describe a novel mechanism of mitochondrial...

  • Mitochondrial membrane permeabilization produced by PTP, Bax and apoptosis: a 1H-NMR relaxation study. Pouliquen, D.; Bellot, G.; Guihard, G.; Fichet, P.; Meflah, K.; Vallette, F. M. // Cell Death & Differentiation;Feb2006, Vol. 13 Issue 2, p301 

    To analyze the involvement of structured water (bound to macromolecules) in apoptosis-induced mitochondrial outer-membrane permeability, we compared the dynamics of water protons from nuclear magnetic resonance (NMR) data in apoptotic liver mitochondria with that of control mitochondria...

  • Bioenergetics and death. Chernyak, B.V.; Pletjushkina, O.Yu.; Izyumov, D.S.; Lyamzaev, K.G.; Avetisyan, A.V. // Biochemistry (00062979);Feb2005, Vol. 70 Issue 2, p240 

    Specific inhibitors of mitochondrial functions were used in studies on the relation between bioenergetics and programmed cell death. The data of the authors are discussed in the review.

  • Fucoidan Extract Induces Apoptosis in MCF-7 Cells via a Mechanism Involving the ROS-Dependent JNK Activation and Mitochondria-Mediated Pathways. Zhongyuan Zhang; Teruya, Kiichiro; Eto, Hiroshi; Shirahata, Sanetaka // PLoS ONE;2011, Vol. 6 Issue 11, p1 

    Background: Fucoidan extract (FE), an enzymatically digested compound with a low molecular weight, is extracted from brown seaweed. As a natural compound with various actions, FE is attractive, especially in Asian countries, for improving the therapeutic efficacy and safety of cancer treatment....


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics